Involvement of PPARγ in Oxidative Stress-Mediated Prostaglandin E2 Production in SZ95 Human Sebaceous Gland Cells

Peroxisome proliferator-activated receptor gamma (PPARγ) is thought to play a role in sebaceous gland cell function. We previously demonstrated in human epidermoid carcinoma KB cells that UVB irradiation activates PPARγ via the generation of multiple oxidized glycerophosphocholine species with PPARγ ligand activity. UVB-induced cyclooxygenase 2 (COX-2) expression was also shown to be PPARγ-dependent. We therefore reasoned that PPARγ activation and PPARγ-dependent COX-2 expression may occur as a general consequence of oxidative stress. The present studies were designed to examine the effects of the oxidant tert-butylhydroperoxide (TBH) on PPARγ activation and COX-2 expression in SZ95 sebocytes. We first verified that functional PPARγ is expressed and activated by UVB irradiation in these cells. We next demonstrated that TBH increased PPARγ reporter activity in SZ95 sebocytes. Increased COX-2 protein, mRNA expression, and prostaglandin E2 (PGE2) production was observed after TBH or PPARγ agonist treatment. The ability of PPARγ agonists and TBH to induce COX-2 expression and PGE2 production was blocked by pretreatment with the specific PPARγ antagonist GW9662. Finally, TBH and PPARγ agonists failed to elicit a PGE2 response in SZ95 sebocytes stably expressing a dominant-negative PPARγ. This study illustrates the importance of the PPARγ system in regulating cellular responses to oxidative stress.