title: NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis.
abstract: The inflammasomes induce maturation of pro-interleukin-1β (IL-1β) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1β, while it reduced IL-18 expression. Either exogenous IL-1β or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1β. Compared to wild-type mice, NLRP3-/-mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1β and IL-18 production; this phenotype was rescued by exogenous IL-1β or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1β and IL-18 may play a protective role against UC through different mechanisms.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Itani
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.|SAMURAI International GI Research Center, Osaka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nadatani
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimura
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hosomi
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nagami
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamata
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.|SAMURAI International GI Research Center, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.|SAMURAI International GI Research Center, Osaka, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.|SAMURAI International GI Research Center, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000378:metabolism*; D010081:Oxazolone / Q000009:adverse effects*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D010081:Oxazolone; D020170:Caspase 1