IL-15 secreted by keratinocytes induces melanogenesis through STAT3/5 signaling pathway in melan-a melanocytes

Chronic UV irradiation of keratinocytes can cause harmful skin diseases. UVB can cause DNA damage and induce various skin diseases. UVB increases melanin production in mammalian skin. In addition, keratinocytes have been shown to increase the secretion of various cytokines when exposed to UVB. These cytokines are known to affect not only immune cells but also non-immune cells. These inflammatory cytokines are closely related to melanin pigmentation. In this study, we investigated the direct effect of IL-15, a cytokine expressed in keratinocytes, on melanin production in melanocytes. IL-15 belongs to the common gamma chain family, which is known as a pro-inflammatory cytokine. UVB exposure has been demonstrated to upregulate the expression of IL-15 in keratinocytes, and IL-15 secretion has also been confirmed. IL-2R beta (IL-15R beta) and the common gamma chain have been identified as IL-15 receptors in melanocytes. IL-15 treatment promoted the upregulation of melanogenesis-related factors such as MITF, tyrosinase, TRP1, and TRP2 in melanocytes. Phosphorylation activation of STAT3 and STAT5 was activated in a time-dependent manner after IL-15 treatment. When siSTAT3 and siSTAT5b were co-administered with IL-15, the melanin content was significantly reduced compared to when IL-15 was administered alone. These results demonstrate that IL-15 directly affects melanocytes and specifically targets the STAT3/STAT5 signaling pathway to induce melanogenesis. Therefore, targeting the IL-15-mediated pathway may provide an effective strategy for the prevention and treatment of UVB-induced hyperpigmentation disorders.