UVB-/Age-Dependent Upregulation of Inflammatory Factor Interleukin-6 Receptor (IL-6R) in Keratinocytes Stimulates Melanocyte Dendricity

Abstract

Ultraviolet (UV) irradiation stimulates melanogenesis in melanocytes and melanin transfer to keratinocytes, where the former is mediated by pleiotropic factors such as SCF, α-MSH, and endothelin-1 (ET-1) secreted by keratinocytes. Therefore, the interaction between melanocytes and keratinocytes after UVB exposure appears to be critical to stimulating melanogenesis. The factors that are responsible for inflammation, one of the key biological processes, are crucial to forming the chronic inflammatory microenvironment in solar lentigines (hereafter called age spots). While chronic inflammation is thought to be involved in hyperpigmentation, the molecular mechanisms through which microinflammation affects melanocyte activation in age spots have not been elucidated. In our study, immunohistochemical analysis showed that the expression of the inflammatory factor IL-6R is enhanced in age spots. Specifically, in cultured keratinocytes irradiated with 10 mJ/cm2 UVB, the expression of IL-6R was upregulated in UVB exposure- and age-dependent manners, and the co-culture of melanocytes with UVB-irradiated keratinocytes further demonstrated that melanocyte dendrites increased in length and number in a keratinocyte-age-dependent manner. Moreover, the suppression of IL-6R function in keratinocytes by an IL-6R-specific neutralizing antibody, Tocilizumab, inhibited melanocyte dendricity. These results indicate that the age- and UVB-dependent upregulation of IL-6R in keratinocytes stimulates melanocyte dendricity, which may also contribute to excessive melanin deposition in age spots.