Bcl-3 deficiency protects against dextran-sodium sulphate-induced colitis in the mouse

O'Carroll, C., Moloney, G., Hurley, G., Melgar, S., Brint, E., Nally, K., Nibbs, R.J. , Shanahan, F. and Carmody, R.J. (2013) Bcl-3 deficiency protects against dextran-sodium sulphate-induced colitis in the mouse. Clinical and Experimental Immunology, 173(2), pp. 332-342. (doi: 10.1111/cei.12119) (PMID:23607276)

Abstract

Bcl-3 is a member of the IκB family of proteins and is an essential negative regulator of Toll-like receptor induced responses. Recently, a single nucleotide polymorphism associated with reduced Bcl-3 gene expression has been identified as a potential risk factor for Crohn's disease. Here we report that in contrast to the predictions of SNP analysis, patients with Crohn's disease and ulcerative colitis demonstrate elevated Bcl-3 mRNA expression relative to healthy individuals. To further explore the potential role of Bcl-3 in inflammatory bowel disease (IBD) we used the dextran-sodium sulphate (DSS) induced model of colitis in Bcl-3(-/-) mice. We found that Bcl-3(-/-) mice were less sensitive to DSS-induced colitis compared to wild type controls and demonstrated no significant weight loss following treatment. Histological analysis revealed similar levels of oedema and leukocyte infiltration between DSS treated wild type and Bcl-3(-/-) mice but showed that Bcl-3(-/-) mice retained colonic tissue architecture which was absent in wild type mice following DSS treatment. Analysis of the expression of the pro-inflammatory cytokines IL-1β, TNFα and IL-6 revealed no significant differences between DSS-treated Bcl-3(-/-) and wild type mice. Analysis of intestinal epithelial cell proliferation revealed enhanced proliferation in Bcl-3(-/-) mice which correlated with preserved tissue architecture. Our results reveal that Bcl-3 has an important role in regulating intestinal epithelial cell proliferation and sensitivity to DSS induced colitis which is distinct from its role as a negative regulator of inflammation.

• Item Type: Articles
• Additional Information: This is the peer reviewed version of the following article: O'Carroll, C., Moloney, G., Hurley, G., Melgar, S., Brint, E., Nally, K., Nibbs, R.J., Shanahan, F., and Carmody, R.J. (2013) Bcl-3 deficiency protects against dextran-sodium sulphate-induced colitis in the mouse. Clinical and Experimental Immunology, 173(2), pp. 332-342, which has been published in final form at dx.doi.org/10.1111/cei.12119. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Carmody, Dr Ruaidhri and Nibbs, Professor Rob
• Authors: O'Carroll, C., Moloney, G., Hurley, G., Melgar, S., Brint, E., Nally, K., Nibbs, R.J., Shanahan, F., and Carmody, R.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Clinical and Experimental Immunology
• Publisher: Wiley-Blackwell Publishing Ltd.
• ISSN: 0009-9104
• ISSN (Online): 1365-2249
• Copyright Holders: Copyright © 2013 British Society for Immunology
• First Published: First published in Clinical and Experimental Immunology 173(2):332-342
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher