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

Research output: Contribution to journalArticle

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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

Fingerprint

Interleukin-17
Psoriasis
Interleukin-6
Skin
Keratinocytes
Th17 Cells
Interleukin-17 Receptors
Immunohistochemistry
T-Lymphocytes
Intradermal Injections
Messenger RNA
Dermis

Keywords

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

ASJC Scopus subject areas

  • Dermatology

Cite this

Fujishima, S., Watanabe, H., Kawaguchi, M., Suzuki, T., Matsukura, S., Homma, T., ... 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

Involvement of IL-17F via the induction of IL-6 in psoriasis. / Fujishima, Sawa; Watanabe, Hideaki; Kawaguchi, Mio; Suzuki, Takao; Matsukura, Satoshi; Homma, Tetsuya; Howell, Brandon G.; Hizawa, Nobuyuki; Mitsuya, Toshiyuki; Huang, Shau Ku; Iijima, Masafumi.

In: Archives of Dermatological Research, Vol. 302, No. 7, 01.09.2010, p. 499-505.

Research output: Contribution to journalArticle

Fujishima, S, Watanabe, H, Kawaguchi, M, Suzuki, T, Matsukura, S, Homma, T, Howell, BG, Hizawa, N, Mitsuya, T, Huang, SK & Iijima, M 2010, 'Involvement of IL-17F via the induction of IL-6 in psoriasis', Archives of Dermatological Research, vol. 302, no. 7, pp. 499-505. https://doi.org/10.1007/s00403-010-1033-8
Fujishima S, Watanabe H, Kawaguchi M, Suzuki T, Matsukura S, Homma T et al. Involvement of IL-17F via the induction of IL-6 in psoriasis. Archives of Dermatological Research. 2010 Sep 1;302(7):499-505. https://doi.org/10.1007/s00403-010-1033-8
Fujishima, Sawa ; Watanabe, Hideaki ; Kawaguchi, Mio ; Suzuki, Takao ; Matsukura, Satoshi ; Homma, Tetsuya ; Howell, Brandon G. ; Hizawa, Nobuyuki ; Mitsuya, Toshiyuki ; Huang, Shau Ku ; Iijima, Masafumi. / Involvement of IL-17F via the induction of IL-6 in psoriasis. In: Archives of Dermatological Research. 2010 ; Vol. 302, No. 7. pp. 499-505.
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