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From the Department of General Surgery,* Westfalian Wilhelms University, Muenster, Germany; the Department of Molecular and Cellular Physiology,
Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana; and the Department of Urology,
University of Miami Miller School of Medicine, Miami, Florida
There is evidence that inducible nitric-oxide synthase (iNOS)-derived NO contributes to the pathophysiology of intestinal inflammation. The aims of this study were to assess the role of iNOS in the development of dextran sodium sulfate (DSS)-induced colonic inflammation and to define the contribution of tissue-specific iNOS expression to this inflammatory response. Study groups included: 1) wild-type (WT) mice; 2) WT
WT bone marrow chimeras with normal iNOS function; 3) WT
iNOS/ chimeras (with functional blood cell iNOS, but iNOS-deficient tissue); 4) iNOS/
WT chimeras (with iNOS-deficient blood cells, but normal tissue iNOS activity); and 5) iNOS-deficient mice. In WT mice and WT
WT chimeras, DSS-induced colonic inflammation was characterized by bloody diarrhea and a high disease activity index. However, WT
iNOS/ and iNOS/
WT chimeras and iNOS/ mice exhibited an attenuated disease activity index, with parallel changes in histopathology. Colonic myeloperoxidase (MPO) was comparably elevated in DSS-treated WT mice (30.1 ± 1.7) and WT
WT chimeras (29.0 ± 1), whereas MPO was significantly reduced in iNOS/ mice and iNOS/
WT chimeras (9.5 ± 1.7 and 15.6 ± 2.2, respectively). WT
iNOS/ chimeras exhibited the lowest MPO activity (3.7 ± 0.6). Our findings implicate both blood cell- and tissue-derived iNOS in DSS-induced colonic inflammation, with tissue-associated iNOS making a larger contribution to the recruitment of inflammatory cells.
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