title: Interleukin-33 exacerbates acute colitis via interleukin-4 in mice.
abstract: Interleukin-33 (IL-33) and its receptor ST2 are over-expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL33 and ST2 are the primary early genes induced in the inflamed colon of BALB/c mice following dextran sulphate sodium (DSS)-induced experimental ulcerative colitis. Accordingly diarrhoea and DSS-induced colon inflammation were impaired in ST2(-/-) BALB/c mice and exacerbated in wild-type mice by treatment with exogenous recombinant IL-33, associated respectively with reduced and enhanced expression of chemokines (CXCL9 and CXCL10), and inflammatory (IL-4, IL-13, IL-1, IL-6, IL-17) and angiogenic (vascular endothelial growth factor) cytokines in vivo. The exacerbation effect of treatment with recombinant IL-33 on DSS-induced acute colitis was abolished in IL-4(-/-) BALB/c mice. Hence, IL-33 signalling via ST2, by inducing an IL-4-dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Pushparaj
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Mousa
authors.initials: M
authors.lastname: Komai-Koma
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: James
authors.initials: J
authors.lastname: Alexander
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4
keywords: ST2 deficiency; colitis; early interleukin-33 expression; interleukin-4 deficiency