Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1alpha, interleukin-1beta, endothelin-1 and tumour necrosis factor-alpha.
Melanocyte-stimulating hormone (MSH) receptor binding activity and melanocortin-1 receptor (MC1-R) gene expression on normal human melanocytes have been studied as responses to the effects of ultraviolet B (UVB), interleukin-1 (IL-1), endothelin-1 (ET-1) and tumour necrosis factor-alpha (TNF-alpha), which are known as UV sensitive regulators of melanocytic function. MSH receptor (MSH-R) binding activity was upregulated by UVB, IL-1alpha, -1beta and ET-1, but was downregulated by TNF-alpha. Northern blot analysis showed that MC1-R mRNA expression was induced 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, whereas TNF-alpha downregulated the expression. In addition, IL-1alpha and -1beta have a small but real inductive effect on MC1-R mRNA expression. Taken together, our results suggest a model in which higher MC1-R mRNA expression is accompanied by upregulation of MSH-R binding activity, and enhanced by UVB or cytokines sensitive to UVB. Such a regulatory system would enable normal human melanocytes to respond to MSH more efficiently and induce an increase of melanization of the skin through the MSH/MSH-R system after UVB radiation.
Department of Dermatology, Kobe University School of Medicine, 5-1 Kusunoki-cho 7-chome, Chuo-ku, Kobe 650, Japan. funasaka@med.kobe-u.ac.jp
Y
Y
Funasaka
A K
AK
Chakraborty
Y
Y
Hayashi
M
M
Komoto
A
A
Ohashi
M
M
Nagahama
Y
Y
Inoue
J
J
Pawelek
M
M
Ichihashi
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D016207:Cytokines / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays; D015854:Up-Regulation
D016207:Cytokines; D019332:Endothelin-1; D007375:Interleukin-1; D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones