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Interleukin‐33 exacerbates acute colitis via interleukin‐4 in mice
Author(s) -
Pushparaj Peter N.,
Li Dong,
KomaiKoma Mousa,
Guabiraba Rodrigo,
Alexander James,
McSharry Charles,
Xu Damo
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12111
Subject(s) - colitis , exacerbation , ulcerative colitis , immunology , chemokine , inflammation , medicine , immune system , interleukin , cytokine , disease
Summary Interleukin‐33 ( IL ‐33) and its receptor ST 2 are over‐expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL 33 and ST 2 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 ST 2 −/− 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 ( CXCL 9 and CXCL 10), 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 ST 2, by inducing an IL ‐4‐dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.