MODULATION OF MELANOCYTE-STIMULATING HORMONE-RECEPTOR EXPRESSION ON NORMAL HUMAN MELANOCYTES - EVIDENCE FOR A REGULATORY ROLE OF ULTRAVIOLET-B, INTERLEUKIN-1-ALPHA, INTERLEUKIN-1-BETA, ENDOTHELIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA

Melanocyte-stimulating hormone (MSH) receptor binding activity and mel anocortin-1 receptor (MC1-R) gene expression on normal human melanocyt es have been studied as responses to the effects of ultraviolet B (UVB ), interleukin-1 (IL-lj, endothelin-l (ET-1) and tumour necrosis facto r-alpha (TNF-alpha), which are known as UV sensitive regulators of mel anocytic function. MSH receptor (MSH-R) binding activity was upregulat ed by UVB, IL-1 alpha, -1 beta and ET-1, but was downregulated by TNF- alpha. Northern blot analysis showed that MC1-R mRNA expression was in duced 24 h after UVB irradiation in a dose-dependent manner. and that 24-h treatment with ET-1 also induced an expression of MC1-R mRNA, whe reas TNF-alpha downregulated the expression. in addition, IL-1 alpha a nd -1 beta have a small but real inductive effect on MC1-R mRNA expres sion. Taken together, our results suggest a model in which higher MC1- R mRNA expression is accompanied by upregulation of MSH-R binding acti vity, and enhanced by UVB or cytokines sensitive to UVB, Such a regula tory system would enable normal human melanocytes to respond to MSH mo re efficiently and induce an increase of melanization of the skin thro ugh the MSH/MSH-R system after WE radiation.