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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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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.

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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.