IFN-γ inhibits basal and α-MSH-induced melanogenesis

Pigment Cell Melanoma Res. 2014 Mar;27(2):201-8. doi: 10.1111/pcmr.12190. Epub 2013 Nov 25.

Abstract

Inflammatory cytokines are closely related to pigmentary changes. In this study, the effects of IFN-γ on melanogenesis were investigated. IFN-γ inhibits basal and α-MSH-induced melanogenesis in B16 melanoma cells and normal human melanocytes. MITF mRNA and protein expressions were significantly inhibited in response to IFN-γ. IFN-γ inhibited CREB binding to the MITF promoter but did not affect CREB phosphorylation. Instead, IFN-γ inhibited the association of CBP and CREB through the increased association between CREB binding protein (CBP) and STAT1. These findings suggest that IFN-γ inhibits both basal and α-MSH-induced melanogenesis by inhibiting MITF expression. The inhibitory action of IFN-γ in α-MSH-induced melanogenesis is likely to be associated with the sequestration of CBP via the association between CBP and STAT1. These data suggest that IFN-γ plays a role in controlling inflammation- or UV-induced pigmentary changes.

Keywords: IFN-γ; melanogenesis; α-MSH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-gamma / pharmacology*
  • Melanins / biosynthesis*
  • Melanocytes / drug effects
  • Melanocytes / enzymology
  • Melanoma, Experimental / enzymology
  • Melanoma, Experimental / pathology
  • Membrane Proteins / metabolism
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • STAT1 Transcription Factor / metabolism
  • alpha-MSH / pharmacology*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Melanins
  • Membrane Proteins
  • Microphthalmia-Associated Transcription Factor
  • Pag1 protein, mouse
  • Phosphoproteins
  • STAT1 Transcription Factor
  • alpha-MSH
  • Interferon-gamma
  • Monophenol Monooxygenase