INDUCTION OF PROSTAGLANDIN-H SYNTHASE-2 IN HUMAN AIRWAY EPITHELIAL-CELLS EXPOSED TO RESIDUAL OIL FLY-ASH

Exposure to ambient air containing respirable particulate matter at co ncentrations below the current National Ambient Air Quality Standard h as been associated with increased rates of pulmonary-related morbidity and mortality. To identify mechanisms involved in pulmonary responses to such exposure, we studied the effects of the emission source parti culate air pollutant residual oil fly ash (ROFA) on prostaglandin meta bolism in cultured human airway epithelial cells. Epithelial cells exp osed to ROFA for 24 hr secreted substantially increased amounts of the prostaglandin H synthase (PHS) products prostaglandins E(2) and F-2 a lpha. The ROFA-induced increase in prostaglandin synthesis was correla ted with a marked increase in PHS activity. Western blots showed that ROFA exposure induced dose-dependent increases in PHS2 protein levels. Reverse transcriptase-PCR analyses demonstrated accompanying increase s in PHS2 mRNA which were evident by 2 hr of continuous exposure. In c ontrast, expression of PHS1 was not affected by ROFA treatment of airw ay epithelial cells. There were no alterations in arachidonic acid rel ease, incorporation, or availability in ROFA-exposed cells. These data show that exposure to ROFA induces PHS2 expression, leading to increa sed prostaglandin synthesis in cultured airway epithelial cells. These findings suggest that prostaglandins may play a role in the toxicolog y of air pollution particle inhalation. (C) 1996 Academic Press, Inc.