Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis.
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.
Watanabe
Hideaki
H
Department of Dermatology, Showa University School of Medicine, Tokyo, Japan. aki2516w@cj8.so-net.ne.jp
Kawaguchi
Mio
M
Fujishima
Sawa
S
Ogura
Miyoko
M
Matsukura
Satoshi
S
Takeuchi
Hiroko
H
Ohba
Motoi
M
Sueki
Hirohiko
H
Kokubu
Fumio
F
Hizawa
Nobuyuki
N
Adachi
Mitsuru
M
Huang
Shau-Ku
SK
Iijima
Masafumi
M
D000818:Animals; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010766:Phosphorylation; D011565:Psoriasis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D020381:Interleukin-17; D016209:Interleukin-8; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3