Role of PPARγ in COX-2 Activation in Mycobacterial Pulmonary Inflammation

Preliminary studies show that intranasal (i.n.) administration of BCG in mice induces M1 activation of alveolar macrophages (Ma...) that increase TNF-alpha production and cyclooxygenase-2 (COX-2) expression but reduce constitutive peroxisome proliferator-activated receptor gamma (PPAR gamma) expression. However, COX-2 is catalytically inactive for prostaglandin E-2 release, unlike COX-2 that is active in M1 activation in vitro by BCG. In this study, we determined the role of PPAR gamma for BCG-induced M1 activation in vivo and in vitro. We found that treatment of mice with GW9662, a PPAR gamma antagonist, prior to i.n. BCG, partially restored PPAR gamma expression, and decreased TNF-alpha production and COX-2 expression. But COX-2 was still inactive. The decreased effects on TNF-alpha and COX-2 were also observed when alveolar Ma... were treated in vitro with GW9662/BCG, but COX-2 was still active. Our results indicate that PPAR gamma upregulates M1 activation of alveolar Ma..., but inactive COX-2 formation is independent of PPAR gamma in mycobacterial pulmonary inflammation.