308 Particulate matter promotes melanin production via endoplasmic reticulum stress

Abstract

Ambient particulate matter (PM), one of the main component of air pollutants, is a major concern for human health, because it is closely associated with mortality and morbidity from respiratory and cardio- and neuro-vascular diseases. Recently, it has been reported that PM can aggravate allergic skin diseases by affecting skin barrier or inducing inflammation. However, it is unclear if PM can induce melanogenesis and which process is involved in PM-mediated melanogenesis. This study investigated the effect of PM on pigmentation and involved mechanism for PM-induced melanogenesis. The effect of PM on melanin production was evaluated in in vitro melanocytes, in vivo mouse skin and ex vivo human skin. The penetration of PM into the skin was examined with cross-sectional multimodal nonlinear optics (MNLO) imaging. Target molecules in PM-mediated pigmentation were screened out through RNA sequencing and the candidate molecules were verified. PM-exposed melanocytes exhibited increased melanin production along with upregulation of tyrosinase and MITF. Phosphorylation of CREB and CAMKII was increased by treatment with PM. Ex vivo and in vivo skin tissues showed increased melanin production following PM treatment. MNLO imaging confirmed that PM actually penetrated into the human skin when barrier dysfunction was induced by tape stripping. RNA-sequencing data revealed that PM treatment to melanocytes induced the expression of endoplasmic reticulum (ER) stress and unfolded protein response (UPR)- related genes among several candidate genes. In particular, the role of ER stress- related molecules in PM-induced melanogenesis was evaluated in this study. These data suggest that PM might induce melanogenesis by affecting ER stress-related genes.