Studies using PPARγagonists in mouse skin have suggested that peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγagonists. UVB is also a potent inducer of prostaglandinE2 (PGE2)production and COX-2 expression in keratinocytes and PPARγis coupled to increasedPGE2production in other cell lines. In this current study, we demonstrate that PPARγagonists, but not PPARαor PPARβ/δagonists, inducePGE2production and COX-2 expression in primary human keratinocytes (PHKs). Importantly, PPARγagonist-induced COX-2 expression andPGE2production were partially inhibited by the PPARγantagonist, GW9662, indicating that both PPARγ-dependent and -independent pathways are likely involved. GW9662 also suppressed UVB andtert-butylhydroperoxide- (TBH-) inducedPGE2production in PHKs and intact human epidermis and partially inhibited UVB-induced COX-2 expression in PHKs. These findings provide evidence that PPARγis relevant to cutaneous photobiology in human epidermis.
Epidermal Peroxisome Proliferator-activated Receptor γ as a Target for Ultraviolet B Radiation
