TY - JOUR
T1 - Interleukin-33 exacerbates acute colitis via interleukin-4 in mice
AU - Pushparaj, Peter N.
AU - Li, Dong
AU - Komai-Koma, Mousa
AU - Guabiraba, Rodrigo
AU - Alexander, James
AU - McSharry, Charles
AU - Xu, Damo
N1 - This is the accepted version of the following article: Pushparaj, P. N., Li, D., Komai-Koma, M., Guabiraba, R., Alexander, J., McSharry, C. and Xu, D. (2013), Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology, 140: 70–77. doi: 10.1111/imm.1211, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/imm.12111/abstract
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - colitis
KW - early interleukin-33 expression
KW - interleukin-4 deficiency
KW - ST2 deficiency
UR - http://www.scopus.com/inward/record.url?scp=84878642267&partnerID=8YFLogxK
U2 - 10.1111/imm.12111
DO - 10.1111/imm.12111
M3 - Article
C2 - 23582173
VL - 140
SP - 70
EP - 77
JO - Immunology
JF - Immunology
SN - 0019-2805
IS - 1
ER -
