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Influence of Slc11a1 (formerly Nramp1) on DSS-induced colitis in mice

Jiang, Hui-Rong and Gilchrist, Derek S and Popoff, Jean-Francois and Jamieson, Sarra E and Truscott, Martha and White, Jacqueline K and Blackwell, Jenefer M (2009) Influence of Slc11a1 (formerly Nramp1) on DSS-induced colitis in mice. Journal of Leukocyte Biology, 85 (4). pp. 703-10. ISSN 1938-3673

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Abstract

Multiple genetic studies in humans indicate a role for solute carrier family 11a member 1 [SLC11A1; formerly natural resistance-associated macrophage protein 1 (NRAMP1)] in autoimmune disease susceptibility, including ulcerative colitis. Murine Slc11a1 has many pleiotropic effects on macrophage activation and proinflammatory responses. To determine which of these are important in ulcerative colitis, we established a phenotype for oral dextran sulfate sodium (DSS)-induced acute colitis in congenic Slc11a1 wild-type (wt) and mutant (mt) mice on a B10 background. For over 7 days of treatment with 2% DSS in the drinking water, Slc11a1 wt mice showed enhanced acute ulcerative colitis, as demonstrated by significantly greater body weight loss and reduction in colon length, as well as a marked increase in monocyte/macrophage inflammatory infiltrates and histopathology changes in the colon. This was accompanied by a clear, inverse relationship between IFN-gamma and IL-10 responses in Slc11a1 wt compared with mt mice, resulting in a significantly higher ratio of IFN-gamma:IL-10 in wt compared with mt mice in lymph node and splenic T cells. RNase protection assays confirmed the presence of significantly higher IFN-gamma at the RNA level in the colons of wt compared with mt mice at Day 7 of treatment. Interestingly this was accompanied by significantly enhanced RNA levels for the acute-phase protein IL-6, which is known to inhibit the generation of forkhead box P3+ regulatory T cells and help to drive the differentiation of Th17 from naive T cells and not by differences in RNA for IL-12p35 or IL-12p40 molecules that dimerize to form the Th1-inducing cytokine IL-12.

Item type: Article
ID code: 32767
Keywords: animals, cation transport proteins, colitis, dextran sulfate, interferon-gamma, interleukin-10, lymph nodes, mice, spleen, Therapeutics. Pharmacology, Cell Biology, Immunology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 24 Aug 2011 13:08
    Last modified: 05 Sep 2014 10:17
    URI: http://strathprints.strath.ac.uk/id/eprint/32767

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