Oncotarget

Research Papers:

Interleukin 1 is a key driver of inflammatory bowel disease-demonstration in a murine IL-1Ra knockout model

Rasha H. Dosh, Nicola Jordan-Mahy, Christopher Sammon and Christine Le Maitre

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Oncotarget. 2019; 10:3559-3575. https://doi.org/10.18632/oncotarget.26894

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Abstract

Rasha H. Dosh1,3, Nicola Jordan-Mahy1, Christopher Sammon2 and Christine Le Maitre1

1 Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK

2 Materials and Engineering Research Institute, Sheffield Hallam University, Sheffield, UK

3 Department of Anatomy and Histology, Faculty of Medicine, University of Kufa, Kufa, Iraq

Correspondence to:

Christine Le Maitre,email: c.lemaitre@shu.ac.uk

Keywords: IL-1Ra deficient; inflammatory bowel disease; pro-inflammatory cytokines; matrix-degrading enzymes; intestinal enzymes

Received: October 23, 2018     Accepted: April 03, 2019     Published: May 28, 2019

ABSTRACT

Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). The balance between IL-1 and IL-1Ra as a natural inhibitor plays a vital role in a variety of diseases. Here, we investigated whether changes seen during IBD are induced spontaneously in mice lacking a functional IL-1rn gene. Histological staining was performed on the jejunum and ileum of BALB/c IL-1rn+/+ and IL-1rn-/- mice to characterize crypt-villus height, villus width, and number of goblet cells per villus. Pro-inflammatory cytokines, immune cell infiltration and matrix-degrading enzymes, together with the production of intestinal enzymes and the integrity of tight and adherent junction proteins were determined using immunohistochemistry. In the small intestine of BALB/c IL-1rn-/- mice the villus heights were significantly reduced; and in the ileum this was accompanied by a decrease in villi width. There was also an increase in goblet cell number and mucin production compared to wild-type mice. IL-1α and IL-1β immunopositivity were increased, whilst IL-1R1 expression was decreased in IL-1rn-/- mice. IL-15 and TNFα were also increased in older IL-1rn-/- mice. Increased polymorphonuclear and macrophage infiltration were seen in IL-1rn-/- mice, whilst expression of matrix-degrading enzymes and digestive enzymes were unchanged, except for dipeptidyl peptidase IV which was increased in younger IL-1rn-/- mice compared to wild type mice. The expression of tight and adhesion junctions were also dramatically decreased in IL-1rn-/- mice. In conclusion, IL-1rn-/- mice developed spontaneous abnormalities which displayed features associated with IBD, demonstrating a clear role for IL-1 in IBD.


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