Melanocyte-stimulating properties of secretory phospholipase A2.

Phospholipase A2 (PLA2) catalyzes the release of free fatty acids from membrane phospholipids, and its products derived from these fatty acids, such as prostaglandins and leukotrienes, significantly up-regulate the key melanogenic enzyme, tyrosinase, in melanocytes. This has led to suggestions that PLA2 itself triggers melanin synthesis in melanogenesis following UV irradiation or inflammation. We have examined the effect of secretory PLA2 (sPLA2) on melanogenesis in cultured human melanocytes. Secretory PLA2 stimulated DNA synthesis and melanin synthesis, and these phenomena were completely inhibited by treatment with a phospholipase inhibitor, p-bromophenacyl bromide, demonstrating that the catalytic activity of sPLA2 is required for melanogenesis. Secretory PLA2 also stimulated tyrosinase activity, increased the amount of tyrosinase-related protein-1 and up-regulated the expression of both mRNA. These findings suggest that sPLA2 is an important mediator of UV-induced or postinflammatory pigmentation.