Increased expression of cyclooxygenase 2 mediates oil fly ash-induced lung injury

We have previously shown that in vitro exposure to the combustion-derived ambient air pollutant residual oil fly ash (ROFA) induces the expression of prostaglandin H synthase 2 (COX2) in human airway epithelial cells. To determine the role of prostaglandins and COX2 expression in ROFA-induced lung injury in vivo, we have examined the effect of intratracheal ROFA instillation on COX2 expression, prostaglandin synthesis, and indices of pulmonary injury and inflammation in adult Sprague-Dawley rats. ROFA treatment induced a marked increase in the level of prostagladin E2 (PGE2) recovered in the bronchoalveolar lavage fluid (BALF), which was effectively decreased by pretreating the animals with the specific COX2 inhibitor NS398. Immunohistochemical analyses of rat airways showed concomitant expression of COX2 in the proximal airway epithelium of rats treated with ROFA. Increases in BALF protein, but not interleukin 6 (IL-6) increases or ROFA-induced polymorphonuclear neutrophils (PMN) influx into the airway, were blunted by administration of NS398 prior to ROFA instillation. These data demonstrate that prostaglandins mediate lung injury induced by exposure to ROFA and implicate increased expression of COX2 as a mechanism that contributes to the toxicity of metal-laden ambient particulate matter.