Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation.
OBJECTIVE
Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in colitis. The objective of this study was to examine the role of iNOS using iNOS-deficient mice in experimental colitis.


METHODS
Colitis was induced by intrarectal instillation of 3% acetic acid and assessed for neutrophilic infiltration and intestinal injury over 7 days. iNOS messenger RNA expression was also measured.


RESULTS
At 24 hours, acetic acid induced a mild colitis in wild-type mice. An increase in neutrophil infiltration and tissue edema was also observed. In the iNOS-deficient mice, a twofold increase in macroscopic damage was observed. Neutrophil infiltration and tissue edema were similar to those in wild-type animals at this time point. Although inflammation in wild-type mice had resolved by 7 days, a sevenfold increase in damage score and elevated myeloperoxidase level were still evident in iNOS-deficient mice. A striking increase in the message for iNOS was observed in inflamed wild-type mice at 24 hours and was still present at 72 hours. No message was found in iNOS-deficient mice.


CONCLUSIONS
Induction of iNOS seems to be a critical protective response to injury in intestinal inflammation possibly by reducing leukocytic infiltration.
McCafferty
D M
DM
Gastrointestinal and Immunology Research Groups, University of Calgary, Alberta, Canada.
Mudgett
J S
JS
Swain
M G
MG
Kubes
P
P
D000818:Animals; D003092:Colitis / Q000209:etiology*; D004790:Enzyme Induction; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D009195:Peroxidase; D019001:Nitric Oxide Synthase