Final Report: Immunologic Basis of Environmental Lung Disease

EPA Grant Number: R825702
Center: Environmental Lung Disease Center (National Jewish Medical and Research Center)
Center Director: Mason, Robert J.
Title: Immunologic Basis of Environmental Lung Disease
Investigators: Mason, Robert J. , White, Carl W. , Gelfand, Erwin , Rabinovitch, Nathan
Institution: National Jewish Medical and Research Center
EPA Project Officer: Chung, Serena
Project Period: February 16, 1998 through February 28, 2003 (Extended to February 28, 2004)
Project Amount: $7,269,177
RFA: Environmental Lung Disease Center (National Jewish Medical and Research Center) (1998) RFA Text |  Recipients Lists
Research Category: Targeted Research

Objective:

The overall objectives of this research project were to: (1) define the effect of winter air pollution, predominately particulates, on children with severe asthma; (2) determine the effect of diesel emissions and ozone in Denver on a murine model of allergen-induced airway hyperresponsiveness; and (3) define the direct effects of ozone on lung epithelial cells. The main clinical project was on children with severe asthma because we felt that they were a special susceptible population, and we wanted to study patients with pre-existing lung disease.

We chose asthma because of the known adverse effects of air pollution on asthmatic patients and because of a unique opportunity in Denver to study a group of asthmatic children in a controlled environment with an opportunity to monitor exposure, symptoms, physiologic function, and medication use. In addition, we have an extensive research program in asthma and in future years can determine the mechanisms whereby different pollutants affect the respiratory and immune systems and alter airway responsiveness. Because of the unique opportunity of having a school for children with severe asthma on our campus, we could compare exposure to the clinical status in a very knowledgeable and responsive patient population. We also could define misclassification of exposures by comparing community standards to those onsite and to personal monitors used by the children at home.

Denver has a special climate and elevation that is representative of other Rocky Mountain cities but is different from U.S. coastal cities. Because of the altitude, for any given amount of work there is increased minute ventilation, which means more exposure to air pollutants. Furthermore, for any given level of lung impairment caused by chronic obstructive lung disease, there is more hypoxemia and pulmonary hypertension in Denver. These conditions cannot be simulated at sea level. Hence, studies in Denver will complement similar studies at sea level, and studies of susceptible populations of patients in Denver may uncover adverse health effects that may not be apparent at sea level.

Detection, assessment, and treatment of adverse health effects caused by air pollution require an understanding of mechanism. National Jewish Medical and Research Center uniquely affords the opportunity of bringing new expertise to bear for determining the mechanism of the effects of air pollutants individually or in combination on the initiation or modulation of the pulmonary inflammatory response. The advent of murine genetics and the opportunity of creating transgenic and gene knockout mice provide an opportunity to investigate the mechanism of injury, inflammation, and host response to air pollutants. In mice, we also can investigate the interactions between air pollution, allergic responses, viral infections, pulmonary inflammation, and lung function.

The final area of focus was on the effect of ozone on pulmonary epithelial cells. This part of the proposal determined the lipid peroxides that were formed by exposure of pulmonary surfactant and epithelial cells to ozone. The surprising finding was the discovery of bioactive cholesterol epoxides. This was a new finding and a new potential therapeutic target for oxidative injury, especially that caused by ozone.

Summary/Accomplishments (Outputs/Outcomes):

Dr. Gelfand’s project failed to show any enhancement of airway inflammation or airway hyperresponsiveness to diesel exhaust particles. They tried to reproduce published findings but failed to reproduce the findings on enhancement of airway inflammation with diesel particles. Their conclusion was that diesel particles were poor inducers of airway inflammation and airway hyperresponsiveness. This is similar to the finding of Dr. Mason that ambient air particles did not increase serum pulmonary surfactant protein D. Hence, particles likely have a very low level of toxicity. This conclusion has been made by other researchers previously.

Dr. Gelfand’s studies with ozone were much more successful, although the dose used to induce a murine response in a small number of animals was above ambient levels of ozone. A 3-hour exposure of greater than 0.5 ppm produced a reproducible neutrophil influx, epithelial injury, and airway hyperresponsiveness. These effects were transient, however, and repair was seen at 24-48 hours. These acute effects were dependent on complement activation and were associated with an increase in IL-1β expression.

Dr. Rabinovitch sought to determine if winter air pollution, especially particulates, would worsen asthma in young severe asthma patients. Dr. Rabinovitch compared personal monitoring to local and central fixed monitors and showed that central monitors consistently overestimate personal exposures. Importantly, there also were higher levels of particulate exposures in homes in which there was cigarette smoking than central monitors. Hence, central monitors are relatively poor surrogates for individual person exposures. Use of personal monitors gave a much better indication of exposure as a result of particulates than central monitors. Dr. Rabinovitch also found that there was an association of immediate medication use and particulate concentrations. Hourly measurements, however, were necessary to establish this finding. There was no consistent effect of 24-hour averaged concentrations of particulates and asthma symptoms, medication use, or physiology in this cohort. Dr. Rabinovitch went on to show that urinary leukotriene E4 (LTE4) levels correlated with peak morning fine particulate matter (PM2.5) concentrations.

Dr. White showed that there was a rapid secretion of ATP upon exposure to low levels of ozone in vitro. This process was shown to be caused by vesicular transport. This ATP was a survival signal for epithelial cells. The implication is that stimulation of this pathway or exogenous ATP might mitigate against the effects of ozone. Dr. White and Dr. Murphy showed that oxidation of surfactant or epithelial cells produced biologically active cholesterol epoxides as well as an aldehyde derivative of phosphidylcholine. They went on to show that the oxidized lipid products also were formed in vivo after ozone exposure and could be recovered in lavage. The cholesterol epoxides are a new mediator likely to be responsible, in part, for the lung damage caused by ozone.

Dr. Mason showed that type II cells were much more sensitive than type I cells to ozone and from gene profiling data suggested that this might be related to glutaredoxin expression in type II cells. In both phenotypes that was induction of heat shock protein 70, hemoxygenase, and metallothionein. Neither cell type showed much of a chemokine response at the protein level. In both phenotypes there was increased secretion of chemokines in response to lipopolysaccharide (LPS) or IL-1β, but this effect was not altered by ozone. Preliminary data suggest that the known chemokine response is a result of cell-cell crosstalk with cell injury of a target cell, release of IL-1α, and subsequent secretion of chemokines by neighboring cells.

Conclusions

Ambient particulate exposure of moderately severe asthmatics in Denver does not markedly alter their symptoms, use of medicines, or pulmonary function. Personal monitors or hourly particulate measurements, however, show an effect of a decrease in forced expiratory volume with increasing particulate exposure. There was an increase in inhaled medication use with hourly PM2.5 levels but not with 24-hour averages. Urinary LTE4 levels correlated with morning particulate levels but not with 24-hour levels. Hence, monitoring should include personal monitors as well as rapid response hourly monitors were needed to show any associations with particulate levels in this cohort of severe asthmatic patients.

Ozone produced lipid peroxides in surfactant and in epithelial cells. These peroxides are toxic and may be responsible for the lung damage caused by ozone. Vesicular ATP release after ozone may protect the lungs from injury and is a survival signal. Epithelial cells don’t secrete much chemokine after exposure to ozone and there is no synergy with LPS or IL-1β. There likely is crosstalk, however, between ozone-damaged cells that send a signal (possibly IL-1α) to neighboring cells that, in turn, can produce chemokines.


Journal Articles: 110 Displayed | Download in RIS Format

Other center views: All 132 publications 111 publications in selected types All 110 journal articles
Type Citation Sub Project Document Sources
Journal Article Ahmad A, Ahmad S, Chang L-Y, Schaack J, White CW. Endothelial Akt activation by hyperoxia: role in cell survival. Free Radical Biology and Medicine 2006;40(7):1108-1118. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Ahmad S, Ahmad A, Ghosh M, Leslie CC, White CW. Extracellular ATP-mediated signaling for survival in hyperoxia-induced oxidative stress. The Journal of Biological Chemistry 2004;279(16):16317-16325. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JBC-Full Text HTML
    Exit
  • Abstract: JBC-Abstract
    Exit
  • Other: JBC-Full Text PDF
    Exit
  • Journal Article Ahmad S, Ahmad A, McConville G, Schneider BK, Allen CB, Manzer R, Mason RJ, White CW. Lung epithelial cells release ATP during ozone exposure: signaling for cell survival. Free Radical Biology and Medicine 2005;39(2):213-226. R825702 (Final)
    R825702C014 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Ahmad S, Ahmad A, Schneider BK, White CW. Cholesterol interferes with the MTT assay in human epithelial-like (A549) and endothelial (HLMVE and HCAE) cells. International Journal of Toxicology 2006;25(1):17-23. R825702 (Final)
  • Abstract from PubMed
  • Abstract: Sage-Abstract
    Exit
  • Journal Article Allen CB. An automated system for exposure of cultured cells and other materials to ozone. Inhalation Toxicology 2003;15(10):1039-1052. R825702 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Allen MJ, Harbeck R, Smith B, Voelker DR, Mason RJ. Binding of rat and human surfactant proteins A and D to Aspergillus fumigatus conidia. Infection and Immunity 1999;67(9):4563-4569. R825702 (Final)
    R825702C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ASM-Full Text PDF
    Exit
  • Abstract: ASM-Abstract and Full Text HTML
    Exit
  • Journal Article Allen MJ, Voelker DR, Mason RJ. Interactions of surfactant proteins A and D with Saccharomyces cerevisiae and Aspergillus fumigatus. Infection and Immunity 2001;69(4):2037-2044. R825702 (Final)
    R825702C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ASM-Full Text PDF
    Exit
  • Abstract: ASM-Abstract and Full Text HTML
    Exit
  • Journal Article Allen MJ, Laederach A, Reilly PJ, Mason RJ. Polysaccharide recognition by surfactant protein D: novel interactions of a C-type lectin with nonterminal glucosyl residues. Biochemistry 2001;40(26):7789-7798. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: ACS-Full Text HTML
    Exit
  • Abstract: ACS-Abstract
    Exit
  • Other: ACS-Full Text PDF
    Exit
  • Journal Article Allen MJ, Laederach A, Reilly PJ, Mason RJ, Voelker DR. Arg343 in human surfactant protein D governs discrimination between glucose and N-acetylglucosamine ligands. Glycobiology 2004;14(8):693-700. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: Oxford-Full Text PDF
    Exit
  • Abstract: Oxford-Abstract and Full Text HTML
    Exit
  • Journal Article Bin L-H, Nielson LD, Liu X, Mason RJ, Shu H-B. Identification of uteroglobin-related protein 1 and macrophage scavenger receptor with collagenous structure as a lung-specific ligand-receptor pair. The Journal of Immunology 2003;171(2):924-930. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text PDF
    Exit
  • Abstract: Journal of Immunology-Abstract and Full Text HTML
    Exit
  • Journal Article Born WK, Lahn M, Takeda K, Kanehiro A, O'Brien RL, Gelfand EW. Role of γδ T cells in protecting normal airway function. Respiratory Research 2000;1(3):151-158. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: BMC-Full Text PDF
    Exit
  • Abstract: BMC-Abstract and Full Text HTML
    Exit
  • Journal Article Brown JP, Taube C, Miyahara N, Koya T, Pelanda R, Gelfand EW, Torres RM. Arhgef1 is required by T cells for the development of airway hyperreactivity and inflammation. American Journal of Respiratory and Critical Care Medicine 2007;176(1):10-19. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Cui Z-H, Joetham A, Aydintug MK, Hahn Y-S, Born WK, Gelfand EW. Reversal of allergic airway hyperreactivity after long-term allergen challenge depends on γδ T cells. American Journal of Respiratory and Critical Care Medicine 2003;168(11):1324-1332. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Dakhama A, Kanehiro A, Makela MJ, Loader JE, Larsen GL, Gelfand EW. Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in allergen sensitized and challenged mice. American Journal of Respiratory and Critical Care Medicine 2002;165(8):1137-1144. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Dakhama A, Kraft M, Martin RJ, Gelfand EW. Induction of regulated upon activation, normal T cells expressed and secreted (RANTES) and transforming growth factor-β1 in airway epithelial cells by Mycoplasma pneumoniae. American Journal of Respiratory Cell and Molecular Biology 2003;29(3):344-351. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Dakhama A, Larsen GL, Gelfand EW. Calcitonin gene-related peptide: role in airway homeostasis. Current Opinion in Pharmacology 2004;4(3):215-220. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Abstract: ScienceDirect-Abstract
    Exit
  • Journal Article Dakhama A, Park J-W, Taube C, Chayama K, Balhorn A, Joetham A, Wei X-D, Fan R-H, Swasey C, Miyahara N, Kodama T, Alvarez A, Takeda K, Gelfand EW. The role of virus-specific immunoglobulin E in airway hyperresponsiveness. American Journal of Respiratory and Critical Care Medicine 2004;170(9):952-959. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Dakhama A, Park J-W, Taube C, El Gazzar M, Kodama T, Miyahara N, Takeda K, Kanehiro A, Balhorn A, Joetham A, Loader JE, Larsen GL, Gelfand EW. Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection. American Journal of Physiology-Lung Cellular and Molecular Physiology 2005;288(4):L761-L770. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJP-Full Text PDF
    Exit
  • Abstract: AJP-Abstract and Full Text HTML
    Exit
  • Journal Article Dakhama A, Park J-W, Taube C, Joetham A, Balhorn A, Miyahara N, Takeda K, Gelfand EW. The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus Is critically dependent on the age at first infection and IL-13 production. The Journal of Immunology 2005;175(3):1876-1883. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Fontenot AP, Falta MT, Freed BM, Newman LS, Kotzin BL. Identification of pathogenic T cells in patients with beryllium-induced lung disease. The Journal of Immunology 1999;163(2):1019-1026. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of ImmunologyFull Text PDF
    Exit
  • Journal Article Fontenot AP, Torres M, Marshall WH, Newman LS, Kotzin BL. Beryllium presentation to CD4+ T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease. Proceedings of the National Academy of Sciences of the United States of America 2000;97(23):12717-12722. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: PNAS-Full Text HTML
    Exit
  • Abstract: PNAS-Abstract
    Exit
  • Other: PNASFull Text PDF
    Exit
  • Journal Article Fujita M, Shannon JM, Irvin CG, Fagan KA, Cool C, Augustin A, Mason RJ. Overexpression of tumor necrosis factor-α produces an increase in lung volumes and pulmonary hypertension. American Journal of Physiology-Lung Cellular and Molecular Physiology 2001;280(1):L39-L49. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJP-Full Text HTML
    Exit
  • Abstract: AJP-Abstract
    Exit
  • Other: AJP-Full Text PDF
    Exit
  • Journal Article Fujita M, Shannon JM, Ouchi H, Voelker DR, Nakanishi Y, Mason RJ. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine 2005;31(1):25-33. R825702 (Final)
  • Abstract from PubMed
  • Abstract: Science Direct-Abstract
    Exit
  • Journal Article Gelfand EW, Joetham A, Cui Z-H, Balhorn A, Takeda K, Taube C, Dakhama A. Induction and maintenance of airway responsiveness to allergen challenge are determined at the age of initial sensitization. Journal of Immunology 2004;173(2):1298-1306. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Gelfand EW, Dakhama A. CD8+ T lymphocytes and leukotriene B4: novel interations in the persistence and progression of asthma. Journal of Allergy and Clinical Immunology 2006;117(3):577-582. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Gelfand EW. Pediatric asthma: a different disease. Proceedings of the American Thoracic Society 2009;6(3):278-282. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ATS-Full Text HTML
    Exit
  • Abstract: ATS-Abstract
    Exit
  • Other: ATS-Full Text PDF
    Exit
  • Journal Article Haczku A, Takeda K, Hamelmann E, Loader J, Joetham A, Redai I, Irvin CG, Lee JJ, Kikutani H, Conrad D, Gelfand EW. CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness. American Journal of Respiratory and Critical Care Medicine 2000;161(3):952-960. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Hahn Y-S, Taube C, Jin N, Sharp L, Wands JM, Aydintug MK, Lahn M, Huber SA, O'Brien RL, Gelfand EW, Born WK. Different potentials of γδT cell subsets in regulating airway responsiveness: Vγ1+ cells, but not Vγ4+ cells, promote airway hyperreactivity, Th2 cytokines, and airway inflammation. The Journal of Immunology 2004;172(5):2894-2902. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Hamada K, Goldsmith C-A, Suzaki Y, Goldman A, Kobzik L. Airway hyperresponsiveness caused by aerosol exposure to residual oil fly ash leachate in mice. Journal of Toxicology and Environmental Health-Part A 2002;65(18):1351-1365. R825702 (Final)
    R826779 (Final)
    R827353 (Final)
    R827353C014 (Final)
  • Abstract from PubMed
  • Full-text: Research Gate-Abstract & Full Text HTML
    Exit
  • Abstract: Taylor & Francis-Abstract
    Exit
  • Other: Research Gate-Full Text PDF
    Exit
  • Journal Article Hamelmann E, Takeda K, Haczku A, Cieslewicz G, Shultz L, Hamid Q, Xing Z, Gauldie J, Gelfand EW. Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and airway hyperresponsiveness in IL-4-deficient mice. American Journal of Respiratory Cell and Molecular Biology 2000;23(3):327-334. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Hirano A, Kanehiro A, Ono K, Ito W, Yoshida A, Okada C, Nakashima H, Tanimoto Y, Kataoka M, Gelfand EW, Tanimoto M. Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge. American Journal of Respiratory Cell and Molecular Biology 2006;35(3):366-377. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, Worthen GS. Toll-IL-1 receptor domain-containing adaptor protein Is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli. The Journal of Immunology 2005;175(11):7484-7495. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, Worthen GS. Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium. American Journal of Respiratory Cell and Molecular Biology 2005;32(6):531-539. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Jin N, Taube C, Sharp L, Hahn Y-S, Yin X, Wands JM, Roark CL, O'Brien RL, Gelfand EW, Born WK. Mismatched antigen prepares γδ T cells for suppression of airway hyperresponsiveness. The Journal of Immunology 2005;174(5):2671-2679. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Jin N, Miyahara N, Roark CL, French JD, Aydintug MK, Matsuda JL, Gapin L, O'Brien RL, Gelfand EW, Born WK. Airway hyperresponsiveness through synergy of γδ T cells and NKT cells. The Journal of Immunology 2007;179(5):2961-2968. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Joetham A, Takeda K, Taube C, Miyahara N, Kanehiro A, Dakhama A, Gelfand EW. Airway hyperresponsiveness in the absence of CD4+ T cells after primary but not secondary challenge. American Journal of Respiratory Cell and Molecular Biology 2005;33(1):89-96. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Joetham A, Takada K, Taube C, Miyahara N, Matsubara S, Koya T, Rha YH, Dakhama A, Gelfand EW. Naturally occurring lung CD4+CD25+ T cell regulation of airway allergic responses depends on IL-10 induction of TGF-β. The Journal of Immunology 2007;178(3):1433-1442. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Joetham A, Takeda K, Miyahara N, Matsubara S, Ohnishi H, Koya T, Dakhama A, Gelfand EW. Activation of naturally occurring lung CD4+CD25+ regulatory T cells requires CD8 and MHC I interaction. Proceedings of the National Academy of Sciences of the United States of America 2007;104(38):15057-15062. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: PNAS-Full Text HTML
    Exit
  • Abstract: PNAS-Abstract
    Exit
  • Other: PNAS-Full Text PDF
    Exit
  • Journal Article Joetham A, Matsubara S, Okamoto M, Takeda K, Miyahara N, Dakhama A, Gelfand EW. Plasticity of regulatory T cells: subversion of suppressive function and conversion to enhancement of lung allergic responses. The Journal of Immunology 2008;180(11):7117-7124. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Joetham A, Takeda K, Okamoto M, Taube C, Matsuda H, Dakhama A, Gelfand EW. Antigen specificity is not required for modulation of lung allergic responses by naturally occurring regulatory T cells. The Journal of Immunology 2009;183(3):1821-1827. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Kanehiro A, Takeda K, Joetham A, Tomkinson A, Ikemura T, Irvin CG, Gelfand EW. Timing of administration of anti-VLA-4 differentiates airway hyperresponsiveness in the central and peripheral airways in mice. American Journal of Respiratory and Critical Care Medicine 2000;162(3):1132-1139. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Kanehiro A, Lahn M, Makela MJ, Dakhama A, Fujita M, Joetham A, Mason RJ, Born W, Gelfand EW. Tumor necrosis factor-α negatively regulates airway hyperresponsiveness through γδ T cells. American Journal of Respiratory and Critical Care Medicine 2001;164(12):2229-2238. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Kanehiro A, Ikemura T, Makela MJ, Lahn M, Joetham A, Dakhama A, Gelfand EW. Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. American Journal of Respiratory and Critical Care Medicine 2001;163(1):173-184. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Kanehiro A, Lahn M, Makela MJ, Dakhama A, Joetham A, Rha Y-H, Born W, Gelfand EW. Requirement for the p75 TNF-α receptor 2 in the regulation of airway hyperresponsiveness by γδ T cells. Journal of Immunology 2002;169(8):4190-4197. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Kitamura K, Takeda K, Koya T, Miyahara N, Kodama T, Dakhama A, Takai T, Hirano A, Tanimoto M, Harada M, Gelfand EW. Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation. The Journal of Immunology 2007;178(1):480-488. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Kodama T, Kuribayashi K, Nakamura H, Fujita M, Fujita T, Takeda K, Dakhama A, Gelfand EW, Matsuyama T, Kitada O. Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma. Clinical and Experimental Immunology 2003;131(2):199-205. R825702 (Final)
    R825702C012 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Wiley-Full Text HTML
    Exit
  • Abstract: Wiley-Abstract
    Exit
  • Other: Wiley-Full Text PDF
    Exit
  • Journal Article Koya T, Takeda K, Kodama T, Miyahara N, Matsubara S, Balhorn A, Joetham A, Dakhama A, Gelfand EW. RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge. American Journal of Respiratory Cell and Molecular Biology 2006;35(2):147-154. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Koya T, Kodama T, Takeda K, Miyahara N, Yang ES, Taube C, Joetham A, Park JW, Dakhama A, Gelfand EW. Importance of myeloid dendritic cells in persistent airway disease after repeated allergen exposure. American Journal of Respiratory and Critical Care Medicine 2006;173(1):42-55. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Koya T, Matsuda JL, Takeda K, Matsubara S, Miyahara N, Balhorn A, Dakhama A, Gelfand EW. IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. The Journal of Allergy and Clinical Immunology 2007;119(5):1241-1250. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Koya T, Miyahara N, Takeda K, Matsubara S, Matsuda H, Swasey C, Balhorn A, Dakhama A, Gelfand EW. CD8+ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4+IL-4+ T cells. The Journal of Immunology 2007;179(5):2787-2796. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Kumarathasan P, Blais E, Goegan P, Yagminas A, Guenette J, Adamson IY, Crapo JD, Mason RJ, Vincent R. 90-day repeated inhalation exposure of surfactant protein-C/tumor necrosis factor-α (SP-C/TNF-α) transgenic mice to air pollutants. International Journal of Toxicology 2005;24(1):59-67. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: ResearchGate-Abstract and Full Text
    Exit
  • Abstract: Sage-Abstract
    Exit
  • Journal Article Lahn M, Kanehiro A, Takeda K, Terry J, Hahn Y-S, Aydintug MK, Konowal A, Ikuta K, O'Brien RL, Gelfand EW, Born WK. MHC class I-dependent Vγ4+ pulmonary T cells regulate αβT cell-independent airway responsiveness. Proceedings of the National Academy of Sciences of the United States of America 2002;99(13):8850-8855. R825702 (Final)
  • Abstract from PubMed
  • Full-text: PNAS-Full Text HTML
    Exit
  • Abstract: PNAS-Abstract
    Exit
  • Other: PNAS-Full Text PDF
    Exit
  • Journal Article Larsen GL, White CW, Takeda K, Loader JE, Nguyen DDH, Joetham A, Groner Y, Gelfand EW. Mice that overexpress Cu/Zn superoxide dismutase are resistant to allergen-induced changes in airway control. American Journal of Physiology-Lung Cellular and Molecular Physiology 2000;279(2):L350-L359. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJP-Full Text HTML
    Exit
  • Abstract: AJP-Abstract
    Exit
  • Other: AJP-Full Text PDF
    Exit
  • Journal Article Lee NA, Gelfand EW, Lee JJ. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? The Journal of Allergy and Clinical Immunology 2001;107(6):945-957. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Lee Y-M, Miyahara N, Takeda K, Prpich J, Oh A, Balhorn A, Joetham A, Gelfand EW, Dakhama A. IFN-γ production during initial infection determines the outcome of reinfection with respiratory syncytial virus. American Journal of Respiratory and Critical Care Medicine 2008;177(2):208-218. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Lively TN, Kossen K, Balhorn A, Koya T, Zinnen S, Takeda K, Lucas JJ, Polisky B, Richards IM, Gelfand EW. Effect of chemically modified IL-13 short interfering RNA on development of airway hyperresponsiveness in mice. The Journal of Allergy and Clinical Immunology 2008;121(1):88-94. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Maier LA, Raynolds MV, Young DA, Barker EA, Newman LS. Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease. American Journal of Respiratory and Critical Care Medicine 1999;159(4):1342-1350. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Makela MJ, Kanehiro A, Borish L, Dakhama A, Loader J, Joetham A, Xing Z, Jordana M, Larsen GL, Gelfand EW. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proceedings of the National Academy of Sciences of the United States of America 2000;97(11):6007-6012. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: PNAS-Full Text HTML
    Exit
  • Abstract: PNAS-Abstract
    Exit
  • Other: PNAS-Full Text PDF
    Exit
  • Journal Article Makela MJ, Kanehiro A, Dakhama A, Borish L, Joetham A, Tripp R, Anderson L, Gelfand EW. The failure of interleukin-10-deficient mice to develop airway hyperresponsiveness is overcome by respiratory syncytial virus infection in allergen-sensitized/challenged mice. American Journal of Respiratory and Critical Care Medicine 2002;165(6):824-831. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Makela MJ, Tripp R, Dakhama A, Park J-W, Ikemura T, Joetham A, Waris M, Anderson LJ, Gelfand EW. Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness. The Journal of Allergy and Clinical Immunology 2003;112(5):861-869. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Manzer R, Wang J, Nishina K, McConville G, Mason RJ. Alveolar epithelial cells secrete chemokines in response to IL-1β and lipopolysaccharide but not to ozone. American Journal of Respiratory Cell and Molecular Biology 2006;34(2):158-166. R825702 (Final)
    R825702C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Manzer R, Dinarello CA, McConville G, Mason RJ. Ozone exposure of macrophages induces an alveolar epithelial chemokine response through IL-1alpha. American Journal of Respiratory Cell and Molecular Biology 2008;38(3):318-323. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Mason RJ. Biology of alveolar type II cells. Respirology 2006;11(Suppl 1):S12-S15. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Wiley-Full Text HTML
    Exit
  • Abstract: Wiley-Abstract
    Exit
  • Other: Wiley-Full Text PDF
    Exit
  • Journal Article Matsubara S, Koya T, Takeda K, Joetham A, Miyahara N, Pine P, Masuda ES, Swasey CH, Gelfand EW. Syk activation in dendritic cells is essential for airway hyperresponsiveness and inflammation. American Journal of Respiratory Cell and Molecular Biology 2006;34(4):426-433. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Matsubara S, Li G, Takeda K, Loader JE, Pine P, Masuda ES, Miyahara N, Miyahara S, Lucas JJ, Dakhama A, Gelfand EW. Inhibition of spleen tyrosine kinase prevents mast cell activation and airway hyperresponsiveness. American Journal of Respiratory and Critical Care Medicine 2006;173(1):56-63. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Matsubara S, Takeda K, Kodama T, Joetham A, Miyahara N, Koya T, Swasey CH, Okamoto M, Dakhama A, Gelfand EW. IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN-γ, and natural killer cells. American Journal of Respiratory Cell and Molecular Biology 2007;36(3):324-332. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Matsubara S, Swasey CH, Loader JE, Dakhama A, Joetham A, Ohnishi H, Balhorn A, Miyahara N, Takeda K, Gelfand EW. Estrogen determines sex differences in airway responsiveness after allergen exposure. American Journal of Respiratory Cell and Molecular Biology 2008;38(5):501-508. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Miyahara N, Swanson BJ, Takeda K, Taube C, Miyahara S, Kodama T, Dakhama A, Ott VL, Gelfand EW. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nature Medicine 2004;10(8):865-869. R825702 (Final)
  • Abstract from PubMed
  • Full-text: EBSCO-Full Text PDF
    Exit
  • Abstract: Nature-Abstract
    Exit
  • Journal Article Miyahara N, Takeda K, Kodama T, Joetham A, Taube C, Park J-W, Miyahara S, Balhorn A, Dakhama A, Gelfand EW. Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13. The Journal of Immunology 2004;172(4):2549-2558. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Miyahara N, Takeda K, Miyahara S, Taube C, Joetham A, Koya T, Matsubara S, Dakhama A, Tager AM, Luster AD, Gelfand EW. Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness. The Journal of Immunology 2005;174(8):4979-4984. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Miyahara N, Takeda K, Miyahara S, Matsubara S, Koya T, Joetham A, Krishnan E, Dakhama A, Haribabu B, Gelfand EW. Requirement for leukotriene B4 receptor 1 in allergen-induced airway hyperresponsiveness. American Journal of Respiratory and Critical Care Medicine 2005;172(2):161-167. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Nishina K, Zhang F, Nielsen LD, Edeen K, Wang J, Mason RJ. Expression of CINC-2β is related to the state of differentiation of alveolar epithelial cells. American Journal of Respiratory Cell and Molecular Biology 2005;33(5):505-512. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Ohnishi H, Miyahara N, Dakhama A, Takeda K, Mathis S, Haribabu B, Gelfand EW. Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1. The Journal of Allergy and Clinical Immunology 2008;121(4):864-871. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Okamoto M, Takeda K, Joetham A, Ohnishi H, Matsuda H, Swasey CH, Swanson BJ, Yasutomo K, Dakhama A, Gelfand EW. Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation. The Journal of Experimental Medicine 2008;205(5):1087-1097. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: JEM-Full Text HTML
    Exit
  • Abstract: JEM-Abstract
    Exit
  • Other: JEM-Full Text PDF
    Exit
  • Journal Article Pacheco KA, Tarkowski M, Sterritt C, Negri J, Rosenwasser LJ, Borish L. The influence of diesel exhaust particles on mononuclear phagocytic cell-derived cytokines: IL-10, TGF-β and IL-1β. Clinical and Experimental Immunology 2001;126(3):374-383. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Wiley-Full Text HTML
    Exit
  • Abstract: Wiley-Abstract
    Exit
  • Other: Wiley-Full Text PDF
    Exit
  • Journal Article Pan T, Nielsen LD, Allen MJ, Shannon KM, Shannon JM, Selman M, Mason RJ. Serum SP-D is a marker of lung injury in rats. American Journal of Physiology-Lung Cellular and Molecular Physiology 2002;282(4):L824-L832. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: AJP-Full Text HTML
    Exit
  • Abstract: AJP-Abstract
    Exit
  • Other: AJP-Full Text PDF
    Exit
  • Journal Article Panayiotidis MI, Stabler SP, Allen RH, Ahmad A, White CW. Cigarette smoke extract increases S-adenosylmethionine and cystathionine in human lung epithelial-like (A549) cells. Chemico-Biological Interactions 2004;147(1):87-97. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Panayiotidis MI, Rancourt RC, Allen CB, Riddle SR, Schneider BK, Ahmad S, White CW. Hyperoxia-induced DNA damage causes decreased DNA methylation in human lung epithelial-like A549 cells. Antioxidants & Redox Signaling 2004;6(1):129-136. R825702 (Final)
  • Abstract from PubMed
  • Abstract: Mary Ann Liebert Publishers
    Exit
  • Journal Article Panayiotidis MI, Stabler SP, Ahmad A, Pappa A, Legros Jr LH, Hernandez-Saavedra D, Schneider BK, Allen RH, Vasiliou V, McCord JM, Kotb M, White CW. Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia. Free Radical Biology and Medicine 2006;40(2):348-358. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Panayiotidis MI, Stabler SP, Allen RH, Pappa A, White CW. Oxidative stress-induced regulation of the methionine metabolic pathway in human lung epithelial-like (A549) cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2009;674(1-2):23-30. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Park J-W, Taube C, Joetham A, Takeda K, Kodama T, Dakhama A, McConville G, Allen CB, Sfyroera G, Schultz LD, Lambris JD, Giclas PC, Holers VM, Gelfand EW. Complement activation is critical to airway hyperresponsiveness after acute ozone exposure. American Journal of Respiratory and Critical Care Medicine 2004;169(6):726-732. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Park JW, Taube C, Yang ES, Joetham A, Balhorn A, Takeda K, Miyahara N, Dakhama A, Donaldson DD, Gelfand EW. Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen. The Journal of Allergy and Clinical Immunology 2003;112(6):1078-1087. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract & Full Text HTML
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article Park J-W, Taube C, Swasey C, Kodama T, Joetham A, Balhorn A, Takeda K, Miyahara N, Allen CB, Dakhama A, Kim S-H, Dinarello CA, Gelfand EW. Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone. American Journal of Respiratory Cell and Molecular Biology 2004;30(6):830-836. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text-PDF
    Exit
  • Journal Article Pulfer MK, Taube C, Gelfand E, Murphy RC. Ozone exposure in vivo and formation of biologically active oxysterols in the lung. Journal of Pharmacology and Experimental Therapeutics 2005;312(1):256-264. R825702 (Final)
    R825702C014 (Final)
  • Abstract from PubMed
  • Full-text: JPET-Full Text HTML
    Exit
  • Abstract: JPET-Abstract
    Exit
  • Other: JPET-Full Text PDF
    Exit
  • Journal Article Rabinovitch N, Zhang L, Murphy JR, Vedal S, Dutton SJ, Gelfand EW. Effects of wintertime ambient air pollutants on asthma exacerbations in urban minority children with moderate to severe disease. The Journal of Allergy and Clinical Immunology 2004;114(5):1131-1137. R825702 (Final)
    R825702C013 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Rabinovitch N, Liu AH, Zhang L, Rodes CE, Foarde K, Dutton SJ, Murphy JR, Gelfand EW. Importance of the personal endotoxin cloud in school-age children with asthma. The Journal of Allergy and Clinical Immunology 2005;116(5):1053-1057. R825702 (Final)
    R825702C013 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Rabinovitch N, Strand M, Gelfand EW. Particulate levels are associated with early asthma worsening in children with persistent disease. American Journal of Respiratory and Critical Care Medicine 2006;173(10):1098-1105. R825702 (Final)
    R825702C013 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Rabinovitch N, Liu AH, Zhang L, Foarde K, Rodes CE, Gelfand EW. Increased personal respirable endotoxin exposure with furry pets. Allergy 2006;61(5):650-651. R825702 (Final)
    R825702C013 (Final)
  • Abstract from PubMed
  • Full-text: Wiley-Full Text HTML
    Exit
  • Abstract: Wiley-Abstract
    Exit
  • Other: Wiley-Full Text PDF
    Exit
  • Journal Article Rabinovitch N, Zhang L, Gelfand EW. Urine leukotriene E4 levels are associated with decreased pulmonary function in children with persistent airway obstruction. The Journal of Allergy and Clinical Immunology 2006;118(3):635-640. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Rha Y-H, Taube C, Haczku A, Joetham A, Takeda K, Duez C, Siegel M, Aydintug MK, Born WK, Dakhama A, Gelfand EW. Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness. Journal of Immunology 2002;169(9):5300-5307. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Silkoff PE, Zhang L, Dutton S, Langmack EL, Vedal S, Murphy J, Make B. Winter air pollution and disease parameters in advanced chronic obstructive pulmonary disease panels residing in Denver, Colorado. The Journal of Allergy and Clinical Immunology 2005;115(2):337-344. R825702 (Final)
  • Abstract from PubMed
  • Full-text: JACI-Full Text HTML
    Exit
  • Abstract: JACI-Abstract
    Exit
  • Other: JACI-Full Text PDF
    Exit
  • Journal Article Strand M, Vedal S, Rodes C, Dutton SJ, Gelfand EW, Rabinovitch N. Estimating effects of ambient PM2.5 exposure on health using PM2.5 component measurements and regression calibration. Journal of Exposure Science and Environmental Epidemiology 2006;16(1):30-38. R825702 (Final)
    R825702C013 (Final)
  • Full-text: PAHO-Full Text PDF
    Exit
  • Abstract: Nature-Abstract and Full Text HTML
    Exit
  • Other: Nature-Full Text PDF
    Exit
  • Journal Article Strand M, Hopke PK, Zhao W, Vedal S, Gelfand E, Rabinovitch N. A study of health effect estimates using competing methods to model personal exposures to ambient PM2.5 modeling personal exposures to PM2.5. Journal of Exposure Science and Environmental Epidemiology 2007;17(6):549-558. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Nature-Full Text PDF
    Exit
  • Abstract: Nature-Abstract and Full Text HTML
    Exit
  • Journal Article Sun W, Kesavan K, Schaefer BC, Garrington TP, Ware M, Johnson NL, Gelfand EW, Johnson GL. MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway. Journal of Biological Chemistry 2001;276(7):5093-5100. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Biological Chemistry-Full Text HTML
    Exit
  • Abstract: Journal of Biological Chemistry-Abstract
    Exit
  • Other: Journal of Biological Chemistry-Full Text PDF
    Exit
  • Journal Article Takeda K, Okamoto M, de Langhe S, Dill E, Armstrong M, Reisdorf N, Irwin D, Koster M, Wilder J, Stenmark KR, West J, Klemm D, Gelfand EW, Nozik-Grayck E, Majka SM. Peroxisome proliferator-activated receptor-γ agonist treatment increases septation and angiogenesis and decreases airway hyperresponsiveness in a model of experimental neonatal chronic lung disease. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology 2009;292(7):1045-1061. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Wiley-Full Text HTML
    Exit
  • Abstract: Wiley-Abstract
    Exit
  • Journal Article Taube C, Duez C, Cui Z-H, Takeda K, Rha YH, Park J-W, Balhorn A, Donaldson DD, Dakhama A, Gelfand EW. The role of IL-13 in established allergic airway disease. The Journal of Immunology 2002;169(11):6482-6489. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Taube C, Dakhama A, Rha Y-H, Takeda K, Joetham A, Park J-W, Balhorn A, Takai T, Poch KR, Nick JA, Gelfand EW. Transient neutrophil infiltration after allergen challenge is dependent on specific antibodies and FcγIII receptors. The Journal of Immunology 2003;170(8):4301-4309. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Taube C, Rha Y-H, Takeda K, Park J-W, Joetham A, Balhorn A, Dakhama A, Giclas PC, Holers VM, Gelfand EW. Inhibition of complement activation decreases airway inflammation and hyperresponsiveness. American Journal of Respiratory and Critical Care Medicine 2003;168(11):1333-1341. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Taube C, Nick JA, Siegmund B, Duez C, Takeda K, Rha Y-H, Park J-W, Joetham A, Poch K, Dakhama A, Dinarello CA, Gelfand EW. Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. American Journal of Respiratory Cell and Molecular Biology 2004;30(6):837-843. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Journal Article Taube C, Wei X, Swasey CH, Joetham A, Zarini S, Lively T, Takeda K, Loader J, Miyahara N, Kodama T, Shultz LD, Donaldson DD, Hamelmann EH, Dakhama A, Gelfand EW. Mast cells, FcεRI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant. The Journal of Immunology 2004;172(10):6398-6406. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Taube C, Miyahara N, Ott V, Swanson B, Takeda K, Loader J, Shultz LD, Tager AM, Luster AD, Dakhama A, Gelfand EW. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. The Journal of Immunology 2006;176(5):3157-3164. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Taube C, Thurman JM, Takeda K, Joetham A, Miyahara N, Carroll MC, Dakhama A, Giclas PC, Holers VM, Gelfand EW. Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation. Proceedings of the National Academy of Sciences of the United States of America 2006;103(21):8084-8089. R825702 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: PNAS-Full Text HTML
    Exit
  • Abstract: PNAS-Abstract
    Exit
  • Other: PNAS-Full Text PDF
    Exit
  • Journal Article Taylor MD, Van Dyke K, Bowman LL, Miles PR, Hubbs AF, Mason RJ, Shannon K, Reasor MJ. A characterization of amiodarone-induced pulmonary toxicity in F344 rats and identification of surfactant protein-D as a potential biomarker for the development of the toxicity. Toxicology and Applied Pharmacology 2000;167(3):182-190. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text PDF
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Journal Article Tomkinson A, Cieslewicz G, Duez C, Larson KA, Lee JJ, Gelfand EW. Temporal association between airway hyperresponsiveness and airway eosinophilia in ovalbumin-sensitized mice. American Journal of Respiratory and Critical Care Medicine 2001;163(3):721-730. R825702 (Final)
  • Abstract from PubMed
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article Tomkinson A, Duez C, Cieslewicz G, Pratt JC, Joetham A, Shanafelt M-C, Gundel R, Gelfand EW. A murine IL-4 receptor antagonist that inhibits IL-4-and IL-13-induced responses prevents antigen-induced airway eosinophilia and airway hyperresponsiveness. Journal of Immunology 2001;166(9):5792-5800. R825702 (Final)
    R825702C012 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Immunology-Full Text HTML
    Exit
  • Abstract: Journal of Immunology-Abstract
    Exit
  • Other: Journal of Immunology-Full Text PDF
    Exit
  • Journal Article Uhlson C, Harrison K, Allen CB, Ahmad S, White CW, Murphy RC. Oxidized phospholipids derived from ozone-treated lung surfactant extract reduce macrophage and epithelial cell viability. Chemical Research in Toxicology 2002;15(7):896-906. R825702 (Final)
    R825702C014 (Final)
  • Abstract from PubMed
  • Full-text: ACS-Full Text HTML
    Exit
  • Abstract: ACS-Abstract
    Exit
  • Other: ACS-Full Text PDF
    Exit
  • Journal Article Wands JM, Roark CL, Aydintug MK, Jin N, Hahn Y-S, Cook L, Yin X, Dal Porto J, Lahn M, Hyde DM, Gelfand EW, Mason RJ, O'Brien RL, Born WK. Distribution and leukocyte contacts of γδ T cells in the lung. Journal of Leukocyte Biology 2005;78(5):1086-1096. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Journal of Leukocyte Biology-Full Text HTML
    Exit
  • Abstract: Journal of Leukocyte Biology-Abstract
    Exit
  • Other: Journal of Leukocyte Biology-Full Text PDF
    Exit
  • Journal Article Wang J, Wang S, Manzer R, McConville G, Mason RJ. Ozone induces oxidative stress in rat alveolar type II and type I-like cells. Free Radical Biology & Medicine 2006;40(11):1914-1928. R825702 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Journal Article Zhang F, Pao W, Umphress SM, Jakowlew SB, Meyer AM, Dwyer-Nield LD, Nielsen LD, Takeda K, Gelfand EW, Fisher JH, Zhang L, Malkinson AM, Mason RJ. Serum levels of surfactant protein D are increased in mice with lung tumors. Cancer Research 2003;63(18):5889-5894. R825702 (Final)
    R825702C001 (Final)
  • Abstract from PubMed
  • Full-text: Cancer Research-Full Text HTML
    Exit
  • Abstract: Cancer Research-Abstract
    Exit
  • Other: Cancer Research-Full Text PDF
    Exit
  • Journal Article Zhao W, Hopke PK, Gelfand EW, Rabinovitch N. Use of an expanded receptor model for personal exposure analysis in schoolchildren with asthma. Atmospheric Environment 2007;41(19):4084-4096. R825702 (Final)
  • Full-text: Science Direct-Full Text HTML
    Exit
  • Abstract: Science Direct-Abstract
    Exit
  • Other: Science Direct-Full Text PDF
    Exit
  • Supplemental Keywords:

    air toxics, acute lung injury, air pollutants, airway disease, animal studies, environmental toxicant, exposure, genetic susceptibility, health effects, human exposure, human health risk, lung disease, lung epithelial cells, occupational disease, occupational exposure,, Health, Scientific Discipline, Air, air toxics, Health Risk Assessment, Epidemiology, Risk Assessments, Disease & Cumulative Effects, Biochemistry, Atmospheric Sciences, Biology, health effects, air pollutants, lung disease, acute lung injury, lung epithelial cells, airway disease, human exposure, susceptibility, environmental toxicant, animal studies, human health risk, genetic susceptibility, occupational exposure

    Relevant Websites:

    Progress and Final Reports:

    Original Abstract
  • 1998
  • 1999
  • 2000
  • 2001
  • 2002
  • 2003
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R825702C001 SP-A and SP-D in Environmental Lung Disease
    R825702C003 Adaptation to Nitrogen Dioxide: Role of Altered Glycolytic Pathway Enzyme Expression and NF-κB-Dependent Cellular Defenses Against Apoptosis
    R825702C005 Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
    R825702C006 Particle-Induced Lung Inflammation and Extracellular EC-SOD
    R825702C007 Indoor-Outdoor Relationships of Airborne Particle Count and Endotoxin Concentrations
    R825702C008 The Role of Mitochondrial DNA Mutations in Oxidant-Mediated Lung Injury
    R825702C009 Immunopathogenesis of Hypersensitivity Pneumonitis in the Mouse
    R825702C010 Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
    R825702C011 Latex Antigen Levels During Powdered and Powderless Glove Use
    R825702C012 Adjuvant Effects of Ozone in a Model of Allergen-Induced Airway Inflammation and Hyperresponsiveness
    R825702C013 Acute Exposure to Particulate Air Pollution in Childhood Asthma
    R825702C014 Mechanisms of Ozone Toxicity to the Lung