Involvement of IL-17F via the induction of IL-6 in psoriasis

Sawa Fujishima, Hideaki Watanabe, Mio Kawaguchi, Takao Suzuki, Satoshi Matsukura, Tetsuya Homma, Brandon G. Howell, Nobuyuki Hizawa, Toshiyuki Mitsuya, Shau Ku Huang, Masafumi Iijima

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54 Citations (Scopus)

Abstract

Recently, the important role of T helper 17 (Th17) cells in psoriasis has been clarified; however, the role of IL-17F produced by Th17 cells is still not fully understood. IL-6 exhibits multiple biologic functions, such as regulation of immunological responses including those in psoriatic reactions. Therefore, we examined the production of IL-6 protein in normal human epidermal keratinocytes (NHEKs) stimulated by IL-17F, TNF-α, IL-17A, and IL-17A in combination with TNF-α, and PBS control. We then examined the expression of IL-6 mRNA in mouse skin after intradermal injection of IL-17F. Finally, IL-17F expression in skin biopsy specimens from psoriasis patients was examined by immunohistochemistry. The results showed that IL-17F induced production of IL-6 in NHEKs in a time-dependent manner. This could be attenuated by chimeric inhibitor blocking the IL-17 receptor. The amounts of IL-6 stimulated by IL-17F were much higher than those stimulated by TNF-α or IL-17A. IL-6 was also significantly upregulated via synergistic stimulation with IL-17A plus TNF-α. The expression of IL-6 mRNA 24 h after IL-17F injection in the mouse skin was 3.2-fold higher than that in the control group. Immunohistochemistry of inflammatory cells in the dermis demonstrated a large number of CD4+ T cells showing IL-17F positivity in psoriatic skin lesions, but few or none in non-lesional psoriatic skin. Our results indicate that IL-17F produced by CD4+ T cells causes the inflammation in psoriasis partly through induction of IL-6 in keratinocytes.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalArchives of Dermatological Research
Volume302
Issue number7
DOIs
Publication statusPublished - Sep 1 2010
Externally publishedYes

Keywords

  • IL-17F
  • IL-6
  • Keratinocyte
  • Psoriasis
  • Th17

ASJC Scopus subject areas

  • Dermatology

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  • Cite this

    Fujishima, S., Watanabe, H., Kawaguchi, M., Suzuki, T., Matsukura, S., Homma, T., Howell, B. G., Hizawa, N., Mitsuya, T., Huang, S. K., & Iijima, M. (2010). Involvement of IL-17F via the induction of IL-6 in psoriasis. Archives of Dermatological Research, 302(7), 499-505. https://doi.org/10.1007/s00403-010-1033-8