IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: Potential relevance to psoriasis

Claire Q F Wang, Yemsratch T. Akalu, Mayte Suarez-Farinas, Juana Gonzalez, Hiroshi Mitsui, Michelle A. Lowes, Seth J. Orlow, Prashiela Manga, James G. Krueger

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Inflammation-associated pigmentation changes are extremely common, but the etiology underlying this clinical observation remains elusive. Particularly, it is unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes. We sought to determine how IL-17 and tumor necrosis factor (TNF) influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines, including melanoma mitogens CXCL1 and IL-8. Moreover, IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocyte production of β-defensin 3, an antagonist for melanocortin 1 receptor. When analyzing psoriasis lesions that are known to overexpress IL-17 and TNF, we observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs resulted in a rapid recovery of pigment gene expression in psoriasis lesions. These results demonstrate that IL-17 and TNF can affect both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms.

Original languageEnglish (US)
Pages (from-to)2741-2752
Number of pages12
JournalJournal of Investigative Dermatology
Volume133
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Fingerprint

Interleukin-17
Psoriasis
Melanocytes
Tumor Necrosis Factor-alpha
Pigmentation
Cytokines
Pigments
Skin
Receptor, Melanocortin, Type 1
Defensins
Melanins
Interleukin-8
Keratinocytes
Mitogens
Skin Diseases
Gene expression
Melanoma
Observation
Inflammation
Gene Expression

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Wang, C. Q. F., Akalu, Y. T., Suarez-Farinas, M., Gonzalez, J., Mitsui, H., Lowes, M. A., ... Krueger, J. G. (2013). IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: Potential relevance to psoriasis. Journal of Investigative Dermatology, 133(12), 2741-2752. https://doi.org/10.1038/jid.2013.237

IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis : Potential relevance to psoriasis. / Wang, Claire Q F; Akalu, Yemsratch T.; Suarez-Farinas, Mayte; Gonzalez, Juana; Mitsui, Hiroshi; Lowes, Michelle A.; Orlow, Seth J.; Manga, Prashiela; Krueger, James G.

In: Journal of Investigative Dermatology, Vol. 133, No. 12, 12.2013, p. 2741-2752.

Research output: Contribution to journalArticle

Wang, CQF, Akalu, YT, Suarez-Farinas, M, Gonzalez, J, Mitsui, H, Lowes, MA, Orlow, SJ, Manga, P & Krueger, JG 2013, 'IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: Potential relevance to psoriasis', Journal of Investigative Dermatology, vol. 133, no. 12, pp. 2741-2752. https://doi.org/10.1038/jid.2013.237
Wang, Claire Q F ; Akalu, Yemsratch T. ; Suarez-Farinas, Mayte ; Gonzalez, Juana ; Mitsui, Hiroshi ; Lowes, Michelle A. ; Orlow, Seth J. ; Manga, Prashiela ; Krueger, James G. / IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis : Potential relevance to psoriasis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 12. pp. 2741-2752.
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