Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne?

Abstract

BACKGROUND: The main function of the human sebaceous gland is sebum excretion. Increased sebum levels combined with follicular hyperkeratinization are a prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors (PPARs) are known to control lipid metabolism in several human tissues they have been considered to be involved in the pathogenesis of acne vulgaris. OBJECTIVES: To investigate the effect of activators of PPAR-α (WY14643), PPAR-γ (rosiglitazone) and PPAR-δ (L-165.041) on basal and staurosporine-induced apoptosis in the human sebocyte cell line SZ95 in vitro. METHODS: After defining the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was determined by the release of histone-associated DNA fragments. The underlying signalling events were detected by Western blotting and the use of specific inhibitors against p44/42 and protein kinase B (PKB)/Akt. RESULTS: PPAR activators of all three subsets offer antiapoptotic effects, with L-165.041 being the most potent. This compound induced the activation of PKB/Akt and p44/42, two kinases involved in antiapoptosis and proliferation, respectively. An inhibition of these kinases by specific inhibitors reversed the suppression of histone-associated DNA fragments by L-165.041, indicating that these signalling pathways participate in the observed antiapoptotic effect. CONCLUSIONS: The present data suggest that activators of PPAR, in particular of the δ subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis.