TY - JOUR
T1 - Increased disease activity in eNOS-deficient mice in experimental colitis
AU - Sasaki, M.
AU - Bharwani, S.
AU - Jordan, P.
AU - Elrod, J. W.
AU - Grisham, M. B.
AU - Jackson, T. H.
AU - Lefer, D. J.
AU - Alexander, J. Steven
N1 - Funding Information:
This study was supported in part by grants HL47615 and P02-DK43785 from the National Institutes of Health.
PY - 2003/12/15
Y1 - 2003/12/15
N2 - Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many features of human inflammatory bowel disease (IBD), (leukocyte extravasation, cachexia, and histopathology). Previous studies suggest that the inducible nitric oxide synthase (iNOS) in blood cells or in the endothelium contribute to this injury. However, until now no study has been performed to directly evaluate the role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease activity in wild-type (eNOS+/+) and eNOS-deficient (eNOS-/-) mice in the DSS model of colitis. Administration of DSS induced weight loss, stool blood, and overt histopathology in both mouse strains. Disease activity was dramatically increased in eNOS-/- mice compared to wild types. Histologically, eNOS-deficient mice had greater leukocyte infiltration, gut injury, and expressed higher levels of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an important role in limiting injury to the intestine during experimental colitis and altered eNOS content and/or activity may contribute to human IBD.
AB - Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many features of human inflammatory bowel disease (IBD), (leukocyte extravasation, cachexia, and histopathology). Previous studies suggest that the inducible nitric oxide synthase (iNOS) in blood cells or in the endothelium contribute to this injury. However, until now no study has been performed to directly evaluate the role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease activity in wild-type (eNOS+/+) and eNOS-deficient (eNOS-/-) mice in the DSS model of colitis. Administration of DSS induced weight loss, stool blood, and overt histopathology in both mouse strains. Disease activity was dramatically increased in eNOS-/- mice compared to wild types. Histologically, eNOS-deficient mice had greater leukocyte infiltration, gut injury, and expressed higher levels of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an important role in limiting injury to the intestine during experimental colitis and altered eNOS content and/or activity may contribute to human IBD.
KW - Free radicals
KW - Inflammatory bowel disease
KW - Nitric oxide
KW - eNOS
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U2 - 10.1016/j.freeradbiomed.2003.09.016
DO - 10.1016/j.freeradbiomed.2003.09.016
M3 - Article
C2 - 14680690
AN - SCOPUS:0346996626
SN - 0891-5849
VL - 35
SP - 1679
EP - 1687
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 12
ER -