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

Peter N. Pushparaj, Dong Li, Mousa Komai-Koma, Rodrigo Guabiraba, James Alexander, Charles McSharry, Damo Xu

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalImmunology
Volume140
Issue number1
Early online date12 Aug 2013
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Colitis
Interleukin-4
Dextran Sulfate
Ulcerative Colitis
Chemokine CXCL9
Colon
Chemokine CXCL10
Interleukin-13
Interleukin-17
Interleukin-1
Vascular Endothelial Growth Factor A
Diarrhea
Interleukin-6
Cytokines
Inflammation
Interleukin-33
Genes

Keywords

  • colitis
  • early interleukin-33 expression
  • interleukin-4 deficiency
  • ST2 deficiency

Cite this

Pushparaj, P. N., Li, D., Komai-Koma, M., Guabiraba, R., Alexander, J., McSharry, C., & Xu, D. (2013). Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology, 140(1), 70-77. https://doi.org/10.1111/imm.12111
Pushparaj, Peter N. ; Li, Dong ; Komai-Koma, Mousa ; Guabiraba, Rodrigo ; Alexander, James ; McSharry, Charles ; Xu, Damo. / Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. In: Immunology. 2013 ; Vol. 140, No. 1. pp. 70-77.
@article{aa7c18bb9f854a1caf2e3ef90147ce10,
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.",
keywords = "colitis, early interleukin-33 expression, interleukin-4 deficiency, ST2 deficiency",
author = "Pushparaj, {Peter N.} and Dong Li and Mousa Komai-Koma and Rodrigo Guabiraba and James Alexander and Charles McSharry and Damo Xu",
note = "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",
year = "2013",
month = "9",
doi = "10.1111/imm.12111",
language = "English",
volume = "140",
pages = "70--77",
journal = "Immunology",
issn = "0019-2805",
number = "1",

}

Pushparaj, PN, Li, D, Komai-Koma, M, Guabiraba, R, Alexander, J, McSharry, C & Xu, D 2013, 'Interleukin-33 exacerbates acute colitis via interleukin-4 in mice', Immunology, vol. 140, no. 1, pp. 70-77. https://doi.org/10.1111/imm.12111

Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. / Pushparaj, Peter N.; Li, Dong; Komai-Koma, Mousa; Guabiraba, Rodrigo; Alexander, James; McSharry, Charles; Xu, Damo.

In: Immunology, Vol. 140, No. 1, 09.2013, p. 70-77.

Research output: Contribution to journalArticle

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

VL - 140

SP - 70

EP - 77

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 1

ER -

Pushparaj PN, Li D, Komai-Koma M, Guabiraba R, Alexander J, McSharry C et al. Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology. 2013 Sep;140(1):70-77. https://doi.org/10.1111/imm.12111