Interleukin-33 exacerbates acute colitis via interleukin-4 in mice

Pushparaj, Peter N. and Li, Dong and Komai-Koma, Mousa and Guabiraba, Rodrigo and Alexander, James and McSharry, Charles and Xu, Damo (2013) Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology, 140 (1). pp. 70-77. (https://doi.org/10.1111/imm.12111)

Full text not available in this repository.Request a copy

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.