Involvement of IL-17F via the induction of IL-6 in psoriasis (original) (raw)

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.

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Abbreviations

NHEKs:

Normal human epidermal keratinocytes

IL:

Interleukin

Th:

T helper

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and, in part, by National Institutes of Health (USA) grant RO1 AI-052468.

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Authors and Affiliations

  1. Department of Dermatology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
    Sawa Fujishima, Hideaki Watanabe & Masafumi Iijima
  2. Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
    Mio Kawaguchi & Nobuyuki Hizawa
  3. Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
    Takao Suzuki & Toshiyuki Mitsuya
  4. Department of Respiratory and Allergy Medicine, Showa University School of Medicine, Tokyo, Japan
    Satoshi Matsukura & Tetsuya Homma
  5. Division of Dermatology, University of Toronto, Toronto, ON, Canada
    Brandon G. Howell
  6. Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, USA
    Shau-Ku Huang

Authors

  1. Sawa Fujishima
  2. Hideaki Watanabe
  3. Mio Kawaguchi
  4. Takao Suzuki
  5. Satoshi Matsukura
  6. Tetsuya Homma
  7. Brandon G. Howell
  8. Nobuyuki Hizawa
  9. Toshiyuki Mitsuya
  10. Shau-Ku Huang
  11. Masafumi Iijima

Corresponding author

Correspondence toHideaki Watanabe.

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Fujishima, S., Watanabe, H., Kawaguchi, M. et al. Involvement of IL-17F via the induction of IL-6 in psoriasis.Arch Dermatol Res 302, 499–505 (2010). https://doi.org/10.1007/s00403-010-1033-8

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