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Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin‐1
Author(s) -
Nakamura Tomoya,
Nishibu Akiko,
Yoshida Naoki,
Yasoshima Mitsue,
Anzawa Kazushi,
Watanabe Yasuharu,
Nagai Yoshinori,
Takatsu Kiyoshi,
Ogawa Kazuo,
Mochizuki Takashi
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12931
Subject(s) - syk , zymosan , inflammation , tumor necrosis factor alpha , immunology , chemistry , macrophage , downregulation and upregulation , medicine , tyrosine kinase , signal transduction , biochemistry , in vitro , gene
Trichophyton infection is highly prevalent and tends to be recurrent. Therefore, it is important to develop new therapeutic agents. Previously, we established a mouse model of Trichophyton ‐induced contact hypersensitivity ( CHS ) and demonstrated that dectin‐1 was involved in inflammation induced by trichophytin, the Trichophyton antigen. Here, we used that model to investigate glycyrrhetinic acid ( GA ) from plants of the genus Glycyrrhiza as a potential anti‐inflammatory agent against superficial mycoses. GA suppressed swelling and the expression of inflammatory cytokines, including macrophage inflammatory protein ( MIP )‐2, interleukin ( IL )‐6, tumor necrosis factor ( TNF )‐ α and interferon ( IFN )‐ γ mRNA . Anti‐ MIP ‐2 antibody suppressed trichophytin‐induced inflammation, and antidectin‐1 antibody suppressed zymosan‐induced MIP ‐2 production in keratinocyte cells. These results suggest that MIP ‐2 is produced by dectin‐1 activation and is involved in inflammation associated with CHS to trichophytin. GA also suppressed zymosan‐induced MIP ‐2 and interleukin ( IL )‐8, production in mouse and human macrophages and keratinocytes. Furthermore, GA suppressed the phosphorylation of spleen tyrosine kinase (Syk) and inhibitor of nuclear factor‐kappa B (I κ B α ) and the degradation of I κ B α in zymosan‐simulated RAW 264.7 cells. The results of this study suggest that GA suppresses inflammation induced by trichophytin, partly by the downregulation of Syk phosphorylation.