Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis

Hideaki Watanabe, Mio Kawaguchi, Sawa Fujishima, Miyoko Ogura, Satoshi Matsukura, Hiroko Takeuchi, Motoi Ohba, Hirohiko Sueki, Fumio Kokubu, Nobuyuki Hizawa, Mitsuru Adachi, Shau Ku Huang, Masafumi Iijima

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59 Citations (Scopus)

Abstract

IL-17F is known to be involved in many inflammatory diseases, but its role in skin diseases has not been fully examined. Because IL-8 is involved in many skin diseases such as psoriasis, we investigated the production of IL-8 in normal human epidermal keratinocytes (NHEKs) stimulated by IL-17F, tumor necrosis factor-α (TNF-α), IL-17A, and control using real-time PCR and ELISA. The results showed that IL-17F induced production of IL-8 in NHEKs in a time-dependent manner. Interestingly, the amounts of IL-8 stimulated by IL-17F were much higher than those stimulated by TNF-α or IL-17A. Next, we confirmed that selective mitogen-activated protein kinase kinase inhibitors significantly inhibited IL-17F-induced IL-8 production. Moreover, mouse skin intradermally injected with IL-17F expressed high level of IL-8 mRNA and induced ERK1/2 phosphorylation. Histological examination of mouse skin that was injected with IL-17F revealed marked neutrophilia in dermis and the infiltration was significantly inhibited by anti-IL-8 antibody. Finally, IL-17F expression in skin biopsy samples from psoriasis patients were examined by western blotting and ELISA. IL-17F was upregulated in lesional psoriatic skin compared with nonlesional skin. These results indicate that IL-17F may be involved in psoriasis via, in part, the activation of ERK1/2 and the induction of IL-8 in keratinocytes.

Original languageEnglish
Pages (from-to)650-656
Number of pages7
JournalJournal of Investigative Dermatology
Volume129
Issue number3
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Watanabe, H., Kawaguchi, M., Fujishima, S., Ogura, M., Matsukura, S., Takeuchi, H., Ohba, M., Sueki, H., Kokubu, F., Hizawa, N., Adachi, M., Huang, S. K., & Iijima, M. (2009). Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis. Journal of Investigative Dermatology, 129(3), 650-656. https://doi.org/10.1038/jid.2008.294