HMGB1/RAGE Mediates UVB-Induced Secretory Inflammatory Response and Resistance to Apoptosis in Human Melanocytes

The Journal of Investigative Dermatology
Kun ZhangLynn A Cornelius

Abstract

The major modifiable risk factor in melanomagenesis is UV exposure and mutagenesis of melanocytes. Other UV-induced events that contribute to early tumorigenesis are poorly understood. Herein we show that the repeated exposure of human primary melanocytes to UVB results in a sustained senescence response, increases in expression of signal transducer and activator of transcription 1, MX1, OAS2, and IRF7 proteins of up to 75-fold, and resistance to subsequent UVB-induced apoptosis. In the setting of UVB-induced DNA damage, we detected time-dependent increases in the release of damage-associated molecular patterns such as high-mobility group box 1 (HMGB1). After intermittent UVB exposure, melanocytes treated with the JAK inhibitor ruxolitinib reduced expression of HMGB1 and MX1 as well as activation of JAK1 (pJAK1) and signal transducer and activator of transcription 1 (pSTAT1). In addition, melanocytes expressing small hairpin RNA selective for the HMGB1 receptor, receptor for advanced glycosylation end product (RAGE), exhibited decreased expression of both HMGB1 and MX1 after UVB exposure. The response of small hairpin RAGE-infected cells to human recombinant HMGB1 was blunted with decreased MX1 expression and JAK activation. Fi...Continue Reading

Citations

Dec 2, 2020·International Journal of Molecular Sciences·Olamide T OlaobaEstelle Leclerc
Dec 22, 2020·Pigment Cell & Melanoma Research·Xiuyi WuChengfeng Zhang
Dec 23, 2020·The Journal of Investigative Dermatology·Eleni FitsiouMarco Demaria

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