Involvement of PPAR gamma in oxidative stress-mediated prostaglandin E-2 production in SZ95 human sebaceous gland cells

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