Tobacco smoke-induced skin pigmentation is mediated by the aryl hydrocarbon receptor

Exp Dermatol. 2013 Aug;22(8):556-8. doi: 10.1111/exd.12170. Epub 2013 Jun 27.


It is widely recognized that tobacco smoke causes skin pigmentation. No studies, however, have directly evaluated the mechanisms of the changes in smoker's skin pigmentation. In this study, when cultured with water-soluble tobacco smoke extract, the human epidermal melanocytes grew to a large size and produced more melanins. We evaluated melanocyte activation by quantifying microphthalmia-associated transcription factor (MITF) expression by real-time polymerase chain reaction. MITF expression was significantly and dose-dependently increased by exposure to tobacco smoke extract. The Wnt/β-catenin signalling pathway seemed to mediate the tobacco smoke extract-induced melanocyte activation. Immunocytochemical studies revealed that the activated melanocytes actively expressed aryl hydrocarbon receptors (AhR) around the nuclear membrane. The tobacco smoke extract-induced MITF activation was inhibited by RNA silencing of the AhR. This study provides the evidence that tobacco smoke enhances pigmentation in vitro and that the increase in pigmentation may involve β-catenin- and AhR-mediated mechanisms inside human melanocytes.

Keywords: aryl hydrocarbon receptor; melanocyte; pigmentation; tobacco smoking; β-catenin.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Nucleus / metabolism
  • Gene Expression Regulation*
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Melanocytes / cytology
  • Melanocytes / drug effects
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Nicotiana / metabolism*
  • RNA / metabolism
  • RNA, Small Interfering / metabolism
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Skin Pigmentation / drug effects*
  • Smoke*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism


  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • CTNNB1 protein, human
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • RNA, Small Interfering
  • Receptors, Aryl Hydrocarbon
  • Smoke
  • beta Catenin
  • RNA