title: Interleukin (IL)-18, cooperatively with IL-23, induces prominent inflammation and enhances psoriasis-like epidermal hyperplasia.
abstract: The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia. In the skin of mice treated with IL-23 plus IL-18, the expression of interferon-γ was significantly upregulated and that of chemokine (C-X-C motif) ligand 9 (CXCL9) was synergistically increased. Histologically, strong positive signals of CXCL9 were observed around the infiltrating inflammatory cells. The current results suggest that IL-18 might synergize with IL-23 to induce a T helper 1 immune reaction, without inhibiting the IL-23/IL-17 axis, and thus may aggravate psoriatic inflammation.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimoura
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. hnagai@med.kobe-u.ac.jp.
authors.forename: Hiroshi
authors.identifier: http://orcid.org/0000-0002-3779-9085
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Jimbo
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000276:immunology*
chemical_list: D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D018836:Inflammation Mediators; D020382:Interleukin-18; D053759:Interleukin-23; D007371:Interferon-gamma
keywords: CXCL9; Interferon-γ; Interleukin-18; Interleukin-23; Psoriasis