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ACTIVATION OF THE EGF RECEPTOR SIGNALING PATHWAY IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO UTAH VALLEY PARTICULATE MATTER
Citation:
Wu, W., J. Samet, A J. Ghio, AND R. B. Devlin. ACTIVATION OF THE EGF RECEPTOR SIGNALING PATHWAY IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO UTAH VALLEY PARTICULATE MATTER. AMERICAN JOURNAL PHYSIOLOGICAL LUNG CELL MOLECULAR PHYSIOLOGY. American Journal of Physiology, 281:L483-L489, (2001).
Description:
Exposure to ambient particulate matter (PM) in the Utah Valley (UV) has previously been associated with a variety of adverse health effects. To investigate intracellular signaling mechanisms for pulmonary responses to UV PM inhalation, human primary airway epithelial cells (NHBE) were exposed to aqueous extracts of PM collected from the year before (Y1), during (Y2), and after (Y3) the closure of a local steel mill located in the UV in this study. Transfection with kinase-deficient ERK1 constructs partially blocked UV PM-induced IL-8 promoter reporter activity. The MEK activity inhibitor PD98059 significantly abolished IL-8 released in response to UV PM, as did the EGF receptor kinase inhibitor AG 1478. Western blotting showed UV PM-induced phosphorylation of EGF receptor tyrosine, MEK1/2 and ERK1/2, which could be ablated with AG1478 or PD98059. For all findings the potency of UV PM collected during Y2 was found to be lower relative to that of Y1 and Y3. These data demonstrate that UV PM can induce IL-8 expression through the activation of the EGF receptor signaling.