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

J Invest Dermatol. 2009 Mar;129(3):650-6. doi: 10.1038/jid.2008.294. Epub 2008 Oct 2.


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-alpha (TNF-alpha), 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-alpha 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epidermis / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / physiology*
  • Interleukin-8 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neutrophils / metabolism*
  • Phosphorylation
  • Psoriasis / metabolism*
  • RNA, Messenger / metabolism


  • Interleukin-17
  • Interleukin-8
  • RNA, Messenger
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3