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

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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.

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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
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  2. Hideaki Watanabe
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  11. Masafumi Iijima
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Correspondence to Hideaki 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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  • DOI: https://doi.org/10.1007/s00403-010-1033-8

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