BACKGROUND: Acne is a chronic inflammatory disease in sebaceous glands and pilosebaceous units where excess sebum production and follicular hyperkeratinization are observed. Adapalene, which exerts comedolytic and anti-inflammatory effects, is used for the topical treatment of mild to moderate acne. OBJECTIVE: We examined the effect of adapalene on sebum production and accumulation in sebaceous gland cells (sebocytes). METHODS: The regulation of sebum production was examined by oil red O and nile red staining and the measurement of triacylglycerols (TGs) in differentiated hamster sebocytes. The gene expression and production of diacylglycerol acyltransferase-1 (DGAT-1) and perilipin 1 (PLIN1) were analyzed using real-time PCR and Western blotting, respectively. RESULTS: Adapalene suppressed sebum accumulation as lipid droplets in spontaneously and insulin-differentiated hamster sebocytes. The TG production, and the gene expression and production of DGAT-1, a rate-limiting enzyme of TG biosynthesis, were dose-dependently inhibited by adapalene in insulin-, 5α-dihydrotestosterone- or a peroxisome proliferator activating receptor γ agonist, troglitazone-differentiated hamster sebocytes. In addition, the inhibition of TG production by adapalene interfered with antagonists against nuclear retinoic acid and retinoid X receptors (CD2665 and UVI3006, respectively) in the differentiated sebocytes. Furthermore, the production of PLIN1, a lipid storage droplet protein, was transcriptionally inhibited by adapalene in the differentiated sebocytes. CONCLUSIONS: These results suggest that adapalene exerts an inhibitory action for sebum accumulation due to the suppression of TG and PLIN1 production in differentiated hamster sebocytes. Furthermore, these findings may contribute to a novel understanding of the molecular mechanisms of adapalene for acne treatment and prevention.
BACKGROUND:Acne is a chronic inflammatory disease in sebaceous glands and pilosebaceous units where excess sebum production and follicular hyperkeratinization are observed. Adapalene, which exerts comedolytic and anti-inflammatory effects, is used for the topical treatment of mild to moderate acne. OBJECTIVE: We examined the effect of adapalene on sebum production and accumulation in sebaceous gland cells (sebocytes). METHODS: The regulation of sebum production was examined by oil red O and nile red staining and the measurement of triacylglycerols (TGs) in differentiated hamster sebocytes. The gene expression and production of diacylglycerol acyltransferase-1 (DGAT-1) and perilipin 1 (PLIN1) were analyzed using real-time PCR and Western blotting, respectively. RESULTS:Adapalene suppressed sebum accumulation as lipid droplets in spontaneously and insulin-differentiated hamster sebocytes. The TG production, and the gene expression and production of DGAT-1, a rate-limiting enzyme of TG biosynthesis, were dose-dependently inhibited by adapalene in insulin-, 5α-dihydrotestosterone- or a peroxisome proliferator activating receptor γ agonist, troglitazone-differentiated hamster sebocytes. In addition, the inhibition of TG production by adapalene interfered with antagonists against nuclear retinoic acid and retinoid X receptors (CD2665 and UVI3006, respectively) in the differentiated sebocytes. Furthermore, the production of PLIN1, a lipid storage droplet protein, was transcriptionally inhibited by adapalene in the differentiated sebocytes. CONCLUSIONS: These results suggest that adapalene exerts an inhibitory action for sebum accumulation due to the suppression of TG and PLIN1 production in differentiated hamster sebocytes. Furthermore, these findings may contribute to a novel understanding of the molecular mechanisms of adapalene for acne treatment and prevention.
Authors: Yael Renert-Yuval; Ester Del Duca; Ana B Pavel; Milie Fang; Rachel Lefferdink; Jianni Wu; Aisleen Diaz; Yeriel D Estrada; Talia Canter; Ning Zhang; Annette Wagner; Sarah Chamlin; James G Krueger; Emma Guttman-Yassky; Amy S Paller Journal: J Allergy Clin Immunol Date: 2021-01-13 Impact factor: 14.290