UVB‐Induced Secretion of IL‐1<i>β</i> Promotes Melanogenesis by Upregulating TYR/TRP‐1 Expression In Vitro
Chunyan Yang, Yanni Guo, Wenjuan Wu, Mao‐Qiang Man, Ying Tu, Li He
Abstract
Purpose . Ultraviolet radiation (UVR) is one of the exogenous stimuli increasing melanogenesis. UV light, especially UVB, is also a potent inducer of epidermal cytokine release. This study is aimed at determining the underlying mechanisms by which UVB‐induced cytokines in keratinocytes regulate melanin production in vitro . Methods . Expression levels of mRNA for interleukin‐ (IL‐) 1, IL‐1 β , IL‐6, IL‐10, IL‐17, and tumor necrosis factor‐alpha (TNF‐ α ) were measured using RT‐qPCR at various time points after UVB irradiation in C57BL/6 mice and HaCaT cells. NaOH lysis and L‐dihydroxyphenylalanine (L‐DOPA) oxidation method were used to measure melanin content and tyrosinase (TYR) activity, respectively, in melanoma B16 cells. RT‐qPCR and Western blot were used to assess mRNA and protein levels of microphthalmia‐associated transcription factor (MITF), TYR, tyrosine‐related protein‐1 (TRP‐1), and tyrosine‐related protein‐2 (TRP‐2) in B16 cells. Finally, expression levels of cyclooxygenase‐2 (COX‐2) mRNA and stem cell factor (SCF) in HaCaT cells were measured following knockdown of IL‐1 β using siRNA (siIL‐1 β ). Results . UVB irradiation increased IL‐1 β mRNA expression levels in both C57BL/6 mice and HaCaT cells. The melanin content, TYR activity, and expression levels of TYR and TRP‐1 were all raised when B16 cells were treated with 4 pg/l of IL‐1. Moreover, IL‐1 β also upregulated the expression levels of SCF and COX‐2 in nonirradiated HaCaT cells. Conversely, knockdown of IL‐1 β attenuated UVB irradiation‐induced upregulation of SCF and COX‐2 expression in keratinocytes. Conclusions . UVB‐induced melanogenesis is mediated in part by IL‐1 β , leading to upregulation of the TYR/TRP1 expression in melanoma B16 cells. IL‐1 β can also stimulate the expression of COX‐2 and SCF in HaCaT cells, which in turn increase melanin synthesis in melanocytes. These results suggest that anti‐inflammatory approaches could possibly mitigate UVB‐induced hyperpigmentation.