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Publication : Spontaneously developing chronic colitis in IL-10/iNOS double-deficient mice.

First Author  McCafferty DM Year  2000
Journal  Am J Physiol Gastrointest Liver Physiol Volume  279
Issue  1 Pages  G90-9
PubMed ID  10898750 Mgi Jnum  J:107861
Mgi Id  MGI:3622390 Doi  10.1152/ajpgi.2000.279.1.G90
Citation  McCafferty DM, et al. (2000) Spontaneously developing chronic colitis in IL-10/iNOS double-deficient mice. Am J Physiol Gastrointest Liver Physiol 279(1):G90-9
abstractText  Mice deficient in both inducible nitric oxide synthase (iNOS) and interleukin (IL)-10 (iNOS(-/-)/IL-10(-/-)) were created to examine the role of iNOS in spontaneously developing intestinal inflammation. IL-10(-/-)/iNOS(-/-) mice were compared with IL-10(-/-) (iNOS(+/+)) littermates over 6 mo. RT-PCR, Western blot analysis, and immunohistochemistry were performed to measure iNOS message and protein levels. Plasma nitrate/nitrite (NO(x)) levels were assessed by HPLC. Damage scores (macroscopic and microscopic) and granulocyte infiltration were assessed. At 3-4 wk, IL-10(-/-) and IL-10(-/-)/iNOS(-/-) mice had no signs of colonic inflammation or granulocyte infiltration. Plasma NO(x) levels were not different from controls. By 3-4 mo, IL-10(-/-) mice had increased damage scores and granulocyte infiltration concurrent with increased mRNA and protein synthesis (restricted to the epithelium) for iNOS in intestinal tissues but not other tissues. Plasma NO(x) levels increased fivefold. Interestingly, in the absence of iNOS induction or increased plasma NO(x), iNOS(-/-)/IL-10(-/-) mice had damage and granulocyte infiltration equivalent to those observed in IL-10(-/-) littermates. These data suggest that iNOS does not impact on the development or severity of spontaneous chronic inflammation in IL-10-deficient mice.
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