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SIGNALING MECHANISMS IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO CARBON ULTRAFINE PARTICLES
Citation:
Samet, J M., C. S. Kim, A. Lenz, R Silbajoris, AND I. Jaspers. SIGNALING MECHANISMS IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO CARBON ULTRAFINE PARTICLES. Presented at American Thoracic Society Annual Meeting, Seattle, WA, May 16-21, 2003.
Description:
SIGNALING MECHANISMS IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO CARBON ULTRAFINE PARTICLES
Y.M. Kim, A.G. Lenz, R. Silbajoris, I. Jaspers and J.M. Samet. Department of Environmental Sciences and Engineering and Center for Environmental Medicine, University of North Carolina, Chapel Hill, NC 27599, GSF-Institute for Inhalation Toxicology, Munich, Germany, and National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711.
Epidemiological studies have demonstrated an association between levels of ultrafine particles in the ambient air and morbidity and mortality. We reported previously that exposure of cultured normal human airway epithelial cells (HAEC) to agglomerates of synthetic elemental carbon ultrafine particles (EC) results in increased expression and release of the chemokine IL-8. In the present study we have examined the effects of EC exposure on signaling events linked to IL-8 expression in HAEC. EC used in this study had a diameter of 75 nm and a surface area of 750 cm2/g and were generated from graphite rods by spark discharge. Since NFkB activation is a major determinant of IL-8 expression in HAEC, we examined indices of NFkB activation in EC-exposed HAEC. In experiments that included vanadium and/or TGFa as positive control stimuli, nuclear protein binding to an NFkB response element oligonucleotide, assessed by electromobility shift assay, and degradation of the inhibitory subunit IkBa, as measured by Western blotting, showed no activation of NFkB in HAEC exposed to 66 ug/ml EC 0.5-24 hrs. In contrast, Western blotting analyses using phosphorylation-state specific antibodies demonstrated that HAEC exposed to 66 ug/ml EC for 12 hrs had increased phosphorylation of the mitogen activated protein kinase P38. Total levels of P38 were not changed by HAEC exposure to EC. Additionally, EC treatment of HAEC had no effect on phosphorylation of ERK1/2, another mitogen activated protein kinase. These data suggest that EC exposure specifically induces activation of P38-dependent signaling which may be a mediator of inflammatory responses such as IL-8 expression in HAEC. Specific activation of intracellular signaling pathways may be an important mechanistic feature of EC-induced toxicity in HAEC, leading to adverse health effects in humans exposed to ambient PM . This abstract of a proposed presentation does not necessarily reflect EPA policy.