The Peroxisome Proliferator-Activated Receptor Gamma System Regulates Ultraviolet B-Induced Prostaglandin E-2 Production in Human Epidermal Keratinocytes

Studies using PPAR gamma agonists in mouse skin have suggested that peroxisome proliferator-activated receptor gamma (PPAR gamma) is irrelevant to cutaneous photobiology. However, in several epithelial cell lines, ultraviolet B (UVB) has been shown to induce the nonenzymatic production of oxidized phospholipids that act as PPAR gamma agonists. UVB is also a potent inducer of prostaglandin E-2 (PGE(2)) production and COX-2 expression in keratinocytes and PPAR gamma is coupled to increased PGE(2) production in other cell lines. In this current study, we demonstrate that PPAR gamma agonists, but not PPAR alpha or PPAR beta/gamma agonists, induce PGE(2) production and COX-2 expression in primary human keratinocytes (PHKs). Importantly, PPAR gamma agonist-induced COX-2 expression and PGE(2) production were partially inhibited by the PPAR gamma antagonist, GW9662, indicating that both PPAR gamma-dependent and -independent pathways are likely involved. GW9662 also suppressed UVB and tert-butylhydroperoxide-(TBH-) induced PGE(2) production in PHKs and intact human epidermis and partially inhibited UVB-induced COX-2 expression in PHKs. These findings provide evidence that PPAR gamma is relevant to cutaneous photobiology in human epidermis.