RGD Reference Report - Influence of Slc11a1 (formerly Nramp1) on DSS-induced colitis in mice. - Rat Genome Database

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

Authors: Jiang, HR  Gilchrist, DS  Popoff, JF  Jamieson, SE  Truscott, M  White, JK  Blackwell, JM 
Citation: Jiang HR, etal., J Leukoc Biol. 2009 Apr;85(4):703-10. Epub 2008 Dec 30.
RGD ID: 5684934
Pubmed: PMID:19116231   (View Abstract at PubMed)
DOI: DOI:10.1189/jlb.0708397   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC11A1HumanExperimental Colitis  ISOSlc11a1 (Mus musculus) RGD 
Slc11a1MouseExperimental Colitis  IMP  RGD 
Slc11a1RatExperimental Colitis  ISOSlc11a1 (Mus musculus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc11a1  (solute carrier family 11 member 1)

Genes (Mus musculus)
Slc11a1  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1)

Genes (Homo sapiens)
SLC11A1  (solute carrier family 11 member 1)


Additional Information