Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1002/ibd.21287
Original Basic Science Articles: IRAK-M and DSS-induced Colitis: Original Basic Science Articles

IL‐1 receptor‐associated kinase M downregulates DSS‐induced colitis†

Berglund, Martin PhD Student1,*; Melgar, Silvia PhD2,3; Kobayashi, Koichi S. MD, PhD4; Flavell, Richard A. PhD6; Hörnquist, Elisabeth Hultgren PhD5; Hultgren, Olof H. MD, PhD1,5,7

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Background:: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll‐like receptor (TLR) regulating protein IL‐1 receptor‐associated kinase M (IRAK‐M) using the erosive dextran sulfate sodium (DSS)‐induced model of colitis.

Methods:: IRAK‐M‐competent and ‐incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T‐cell transcription factors.

Results:: At day 7 IRAK‐M‐deficient mice display a reduced total body weight (77.1 ± 2.1 versus 88.5 ± 2.0, *P = 0.002) and an increased macroscopical (2.7 ± 0.2 versus 1.6 ± 0.1, *P = 0.002) and histopathological (6.0 ± 0 versus 3.3 ± 0.5, *P = < 0.001) colon score compared to wildtype mice. Furthermore, IRAK‐M‐deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 ± 13.5 versus 12.8 ± 2.0 pg/mL, *P = 0.010) in plasma.

Conclusions:: This is the first report examining the role of IRAK‐M in colitis. We find that IRAK‐M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK‐M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010)

© Crohn's & Colitis Foundation of America, Inc.

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