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    Contact dermatitis is a form of delayed-type hypersensitivity characterized by localized thickening, papules, redness and vesicles of the skin. A model of contact dermatitis involving repeated challenge of a hapten is adapted to assess dermatitis as characterized by skin thickening. Recently, it was reported that neutrophils have crucial roles in contact hypersensitivity. We thus examined the involvement of CXC chemokines bearing the glutamic acid-leucine-arginine (ELR) motif ("ELR+ chemokines") and neutrophils in the ear swelling induced by 2,4,6-trinitrochlorobenzene (TNCB) challenges in the present study. Mice were sensitized by application of TNCB on their abdominal skin. They were then challenged thrice with TNCB to the ear. The CXCR2 antagonist SB225002 (9 mg/kg, i.p.) was administered before each TNCB challenge. Gene expressions and protein levels of the ELR+ chemokines CXCL1, 2 and 5 was increased markedly in mouse ear after the final TNCB challenge. In addition, we indicated that gene expression of CXCL1 was enhanced in the epidermis and dermis upon TNCB challenge. Expression of the CXCL2 gene was enhanced in the epidermis, and that of the CXCL5 gene was enhanced in the dermis. The swelling induced by TNCB challenges was significantly attenuated by SB225002. Furthermore, the increases in myeloperoxidase activity, and expression of myeloperoxidase and neutrophil elastase induced by TNCB challenge in mouse ear were inhibited by SB225002. These data suggest that ear swelling resulting from TNCB challenges might be concerned by upregulated ELR+ chemokine-induced neutrophil recruitment. © 2017 John Wiley & Sons Australia, Ltd.

    Citation

    Hiroyasu Sakai, Saori Yabe, Ken Sato, Yuki Kai, Fumiaki Sato, Tetsuro Yumoto, Yuka Inoue, Minoru Narita, Kenjiro Matsumoto, Shinichi Kato, Yoshihiko Chiba. ELR+ chemokine-mediated neutrophil recruitment is involved in 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity. Clinical and experimental pharmacology & physiology. 2017 Aug 01


    PMID: 28762515

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