Histamine receptor 2-mediated growth-differentiation factor-15 expression is involved in histamine-induced melanogenesis

Hye Ja Lee, Mi Kyung Park, Eun Ji Lee, You Lee Kim, Hyun Ji Kim, Joon Hee Kang, Hwan Mook Kim, Ai Young Lee, Chang Hoon Lee

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Vitiligo is a progressive depigmenting disorder. Histamine has been shown to induce melanogenesis via histamine receptor 2, suggesting the possibility of histamine as a repigmenting agent for the treatment of vitiligo. However, the role and signaling mechanism of histamine are still unclear in melanogenesis, especially in relation to growth-differentiation factor-15, which is a protein belonging to transforming growth factor beta and found to be overexpressed in metastatic or malignant melanoma. We found that histamine induces growth-differentiation factor-15 in melanoma cell lines such as SK-MEL-2, B16F10, and melan-a cells. Therefore, in the present study, the role of growth-differentiation factor-15 in histamine-induced melanogenesis was investigated using gene silencing or overexpression of growth-differentiation factor-15 and histamine related compounds such as histamine, amthamine, and cimetidine. Gene silencing of growth-differentiation factor-15 suppressed histamine-induced proliferation, melanin production, tyrosinase activity, and chemotactic migration of SK-MEL-2 cells. Histamine-induced expression of tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 was also suppressed by growth-differentiation factor-15 gene silencing. On the other hand, overexpression of growth-differentiation factor-15 using a plasmid containing growth-differentiation factor-15 in SK-MEL-2 cells increased melanin production and chemotactic migration. Amthamine induced expression of growth-differentiation factor-15 in a time and concentration dependent manner. Amthamine-induced expression of growth-differentiation factor-15 was suppressed by cimetidine. Our results suggest that growth-differentiation factor-15 is a new player in histamine-induced melanogenesis, which can help researchers to extend the knowledge of the role of the transforming growth factor beta family in melanogenesis and in skin pigment disorders such as vitiligo.

Original languageEnglish
Pages (from-to)2124-2128
Number of pages5
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • Chemotactic migration
  • Growth-differentiation factor-15
  • Histamine
  • Histamine receptor 2
  • Melanin pigmentation
  • Melanoma cells

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