Increased disease activity in eNOS-deficient mice in experimental colitis
Abstract
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.
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- Authors
- Sasaki, M., Bharwani, S., Jordan, P., Elrod, J. W., Grisham, M. B., Jackson, T. H., Lefer, D. J., & Alexander, J. S.
- Affiliations
- Louisiana State University Health Sciences Center Shreveport (US)
- Corresponding author
- Alexander, J.Steven
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 35
- Issue
- 12
- Pages
- 1679-1687
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2069037824
- Cited by
- 70
- References
- 56
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29hl047615-05)
- National Heart, Lung, and Blood Institute (HL-47615)
- National Institute of Diabetes and Digestive and Kidney Diseases (P02-DK-43785)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- endothelial nitric oxide synthase, eNOS-deficient mice, experimental colitis, DSS-induced colitis, inflammatory bowel disease, disease activity, leukocyte infiltration, MAdCAM-1, intestinal injury, nitric oxide
- MeSH terms
- Animals, Colitis, Colon, Immunoglobulins, Immunohistochemistry, Mucoproteins, Cell Adhesion Molecules, Mice, Knockout, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III
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