title: Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin-1.
abstract: 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 (IκBα) and the degradation of IκBα in zymosan-simulated RAW264.7 cells. The results of this study suggest that GA suppresses inflammation induced by trichophytin, partly by the downregulation of Syk phosphorylation.
authors.affiliation: Department of R&D Center, Ikeda Mohando Co., Ltd, Toyama, Japan.|Department of Dermatology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishibu
authors.affiliation: Department of R&D Center, Ikeda Mohando Co., Ltd, Toyama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of R&D Center, Ikeda Mohando Co., Ltd, Toyama, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Yasoshima
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Anzawa
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan.|Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology, Saitama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan.|Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.affiliation: Department of R&D Center, Ikeda Mohando Co., Ltd, Toyama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002470:Cell Survival; D054426:Chemokine CXCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D006035:Glycyrrhiza; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009181:Mycoses / Q000188:drug therapy; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D010766:Phosphorylation; D000072377:Syk Kinase / Q000378:metabolism; D014248:Trichophytin / Q000009:adverse effects*; D014249:Trichophyton; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000737:chemistry; D000099181:Dectin-1
chemical_list: D000893:Anti-Inflammatory Agents; D054426:Chemokine CXCL2; D016207:Cytokines; D006034:Glycyrrhetinic Acid; D007371:Interferon-gamma; D015850:Interleukin-6; D037181:Lectins, C-Type; D000072000:NF-KappaB Inhibitor alpha; D000072377:Syk Kinase; D014248:Trichophytin; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D000099181:Dectin-1; C000606897:Syk protein, mouse
keywords: Syk; dectin-1; glycyrrhetinic acid; trichophytin-induced inflammation model