Grantee Research Project Results
Final Report: Mechanisms of Particulate-Induced Mediator Expression in Human Airway Epithelial Cells
EPA Grant Number: R826270Title: Mechanisms of Particulate-Induced Mediator Expression in Human Airway Epithelial Cells
Investigators:
Institution: University of North Carolina at Chapel Hill
EPA Project Officer: Chung, Serena
Project Period: December 15, 1997 through December 14, 2000
Project Amount: $374,170
RFA: Health Effects and Exposures to Particulate Matter and Associated Air Pollutants (1997) RFA Text | Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Human Health , Air
Objective:
The objective of this research project was to investigate the effects of respirable fine particulate matter (PM2.5) on human respiratory tract epithelial cells to bridge the gap between human epidemiological and animal toxicological studies. This research project addresses possible biological mechanisms underlying the adverse human health effects associated with exposure to the PM2.5 present in air pollution. Epidemiological studies suggest that humans, especially those with chronic pulmonary or cardiovascular disease, are adversely affected by exposure to PM2.5, and animal toxicological studies have shown that PM2.5 introduced into the respiratory tract causes adverse health effects such as inflammation. The underlying hypothesis of this research is that respirable particulates carry currently unidentified toxic environmental chemicals into the respiratory tract, where they are deposited onto the epithelial cell lining and act to disrupt normal epithelial cell functions, resulting in inflammation.
Summary/Accomplishments (Outputs/Outcomes):
The epithelial cells that line the human respiratory tract present the first
barrier to inhaled pollutants. An additional aim of this research was to determine
how PM2.5 injures or irritates the human respiratory tract. We hypothesized
that PM2.5 evokes proinflammatory or other stress responses in epithelial cells.
We have characterized, at a molecular level, the responses of airway epithelial
cells to a “real world” fine particulate air pollutant, residual
oil fly ash (ROFA). ROFA is known to cause respiratory tract injury and inflammation
in animals and humans. We have shown that exposure of human respiratory tract
epithelial cells to ROFA evokes a proinflammatory response by activating the
Nuclear Factor- B (NF-
B)-dependent signal transduction cascade. ROFA is composed
primarily of metals, with soluble forms of vanadium and iron being the most
abundant. We have found that soluble forms of vanadium, but not iron, elicit
a similar stress response. Vanadium compounds are recognized respiratory tract
irritants. Our findings suggest a biochemical basis for vanadium toxicity in
the respiratory tract by identifying a particular stress response program that
is activated by vanadium. We have shown that enhancing the cell’s antioxidant
defenses reduces the stress response caused by vanadium, suggesting that vanadium
acts by putting the cells under oxidative stress. Our findings suggest that
PM2.5 containing vanadium have the potential to cause adverse health effects
by causing oxidative stress in lung cells. This finding suggests that antioxidants
may protect against the adverse health effects of vanadium and other components
of PM2.5.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
| Other project views: | All 4 publications | 4 publications in selected types | All 4 journal articles |
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Jaspers I, Samet JM, Reed W. Arsenite exposure of cultured airway epithelial cells activates κB-dependent interleukin-8 gene expression in the absence of nuclear factor-κB nuclear translocation. Journal of Biological Chemistry 1999;274(43):31025-31033. |
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Jaspers I, Samet JM, Erzurum S, Reed W. Vanadium-induced κB-dependent transcription depends upon peroxide-induced activation of the p38 mitogen-activated protein kinase. American Journal of Respiratory Cell and Molecular Biology 2000;23(1):95-102. |
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Jaspers I, Zhang W, Fraser A, Samet JM, Reed W. Hydrogen peroxide has opposing effects on IKK activity and IκBα breakdown in airway epithelial cells. American Journal of Respiratory Cell and Molecular Biology 2001;24(6):769-777. |
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Quay JL, Reed W, Samet J, Devlin RB. Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-κB activation. American Journal of Respiratory Cell and Molecular Biology 1998;19(1):98-106. |
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Supplemental Keywords:
ambient air, residual oil fly ash, ROFA, metals, transition metals, oxidants, sulfates, health effects, immunotoxicology, cellular, biology, cell biology, molecular biology, air, health, biochemistry, environmental microbiology, epidemiology, health risk assessment, genetics, air toxics, particulate matter, PM2.5, PM10, airway epithelial cells, animal toxicological studies, biological mechanisms, cardiopulmonary mechanisms, cardiopulmonary responses, chronic health effects, epidemiological studies, exposure and effects, human exposure, human health effects, particle induced mediator expression,, RFA, Health, Air, Scientific Discipline, Health Risk Assessment, Risk Assessments, particulate matter, Environmental Chemistry, Environmental Microbiology, Molecular Biology/Genetics, Biochemistry, Toxicology, air toxics, biological mechanisms, human exposure, cardiopulmonary mechanisms, cardiopulmonary responses, PM10, pulmonary, immunotoxicology, particle induced mediator expression, molecular biology, airway epithelial cells, chronic health effects, human health effects, PM 2.5, animal toxicological studiesProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.