Regulation of Murine Intestinal Inflammation by Reactive Metabolites of Oxygen and Nitrogen
| Autor: | D. Neil Granger, Christopher R. Ross, Janice Russell, James W. Salter, F. Stephen Laroux, Wolfgang H. Cerwinka, Guido Schuermann, Christian F. Krieglstein, Matthew B. Grisham |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences Reactive oxygen species NADPH oxidase biology Superoxide Immunology medicine.disease Molecular biology 3. Good health Nitric oxide Superoxide dismutase Nitric oxide synthase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biochemistry chemistry 030220 oncology & carcinogenesis biology.protein medicine Immunology and Allergy Colitis Nicotinamide adenine dinucleotide phosphate 030304 developmental biology |
| Zdroj: | Journal of Experimental Medicine. 194:1207-1218 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.194.9.1207 |
| Popis: | Several reports have implicated reactive oxygen and nitrogen metabolites (RONS) in the initiation and/or progression of inflammatory bowel diseases (IBDs). We have investigated the role of three key RONS-metabolizing enzymes (inducible nitric oxide synthase [iNOS], superoxide dismutase [SOD], nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in a murine model of IBD. Mice genetically deficient (−/−) in either iNOS or the p47phox subunit of NADPH oxidase, transgenic (Tg) mice that overexpress SOD, and their respective wild-type (WT) littermates were fed dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis. In addition, the specific iNOS inhibitor 1400W was used in DSS-treated WT and p47phox−/− mice. WT mice responded to DSS feeding with progressive weight loss, bloody stools, elevated serum NOX and colonic mucosal injury with neutrophil infiltration. Both the onset and severity of colitis were significantly attenuated in iNOS−/− and 1400W-treated WT mice. While the responses to DSS did not differ between WT and p47phox−/− mice, enhanced protection was noted in 1400W-treated p47phox−/− mice. Interestingly, SODTg mice exhibited more severe colitis than their WT littermates. These findings reveal divergent roles for superoxide and iNOS-derived NO in intestinal inflammation. |
| Databáze: | OpenAIRE |
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