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IL-1 receptor-assoc...
IL-1 receptor-associated kinase M downregulates DSS-induced colitis
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- Berglund, Martin (author)
- Dept Microbiol & Immunol, Inst Biomed, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden
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- Melgar, Silvia (author)
- Alimentary Pharmabiot Ctr, Univ Coll Cork, Cork, Ireland; Immunoinflammat CEDD GlaxoSmithKline, Stevenage Herts, England
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- Kobayashi, Koichi S. (author)
- Harvard Univ, Boston MA, USA
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- Flavell, Richard A. (author)
- Yale Univ, New Haven CT, USA
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- Hultgren Hörnquist, Elisabeth, 1965- (author)
- Örebro universitet,Hälsoakademin
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- Hultgren, Olof H. (author)
- Department of Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Örebro University Hospital, Örebro, Sweden
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(creator_code:org_t)
- Oxford University Press (OUP), 2010
- 2010
- English.
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In: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:10, s. 1778-1786
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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 +/- 60.5, *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; 16: 1778-1786)
Keyword
- IRAK-M
- TLR signaling
- colitis
- proinflammatory cytokines
- MEDICINE
- MEDICIN
- Medicine
- Medicin
Publication and Content Type
- ref (subject category)
- art (subject category)
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