Melasma is a hyper-pigmentary disorder with photoaging features. Since the manifestations appear on specific face areas, rich in sebaceous glands, we explored their possible role in the onset. The gene and protein expression of inflammatory and pro-melanogenic factors from the SZ95 sebaceous gland cell line exposed to single or repetitive UVA doses (2 to 8 J/cm2), as triggering stimulus able to reach the dermis and skin appendages, were evaluated. UVA up-modulated the long-lasting production of α-MSH, EDN1, b-FGF, SCF, inflammatory cytokines, and lipid-derived mediators, through the p53 and PPARγ activation, since the interfering significantly reduced the production. Irradiated SZ95 sebocyte conditioned media increased pigmentation in melanocytes and the expression of senescence markers, pro-inflammatory cytokines, and growth factors regulating melanogenesis in cultured fibroblasts. The combination of UVA irradiation, estrogen, and irradiated SZ95 sebocyte media had a synergistic effect on fibroblast growth factors production. Ex-vivo experiments, using skin explants co-coltured with irradiated SZ95 sebocytes, confirmed their role in modulating skin pigmentation. Moreover, in vivo data demonstrated that pro-melanogenic growth factors level was increased in sebum from lesional versus non-lesional skin, confirming the in vitro studies. Overall, our results indicate sebocytes as playmakers in melasma pathogenesis, inducing prolonged skin cell stimulation, leading to localized dermal aging and hyper-pigmentation. Our data provide new insights into melasma pathogenesis and possible therapies.

ESDR299 - Melasma: a sebocyte-dependent disease?

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING