eNOS plays an important role in the regulation of colonic inflammation: a novel therapeutic target and a predictive marker for the prognosis of ulcerative colitis.
Free Radic Res
; 49(1): 35-44, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25329334
ABSTRACT
BACKGROUND:
We reported that deficiency of the eNOS protein exacerbates colitis induced by dextran sodium sulfate (DSS-induced colitis). However, the role of eNOS in colitis remains controversial. Therefore, we studied how over-expression of eNOS affected this inflammatory condition, using vascular endothelial cells and mice as in vitro and in vivo models, respectively. Furthermore, we investigated the influence of a polymorphism in the eNOS gene on the clinical features of ulcerative colitis (UC).METHODS:
We examined the effect of eNOS overexpression on the expression of adhesion molecules in the endothelium and assessed the degree of DSS-induced colitis in eNOS transgenic (eNOS-Tg) mice. We also investigated the relationship between a polymorphism in the eNOS gene and clinical features of patients with UC.RESULTS:
The expression of adhesion molecules, under inflammatory conditions, was attenuated in eNOS gene-transfected vascular endothelial cells, as measured by western blot analysis. Symptoms of DSS-induced colitis were likewise attenuated in eNOS-Tg mice, which exhibited lower weight loss, mortality, histological damage (by inflammation score and crypt damage score), and colonic myeloperoxidase activity, tumor necrosis factor-α expression, and MAdCAM-1 expression than in wild-type mice. Furthermore, there was a significant relationship between intractable cases of UC and a polymorphism in the eNOS gene promoter (c.-786 T > C) that decreases eNOS expression.CONCLUSION:
The eNOS gene plays an important role in the regulation of colonic inflammation. The level of eNOS expression may be a predictive marker for prognosis of UC, and eNOS expression may be a novel therapeutic target.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colitis Ulcerosa
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Óxido Nítrico Sintasa de Tipo III
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Free Radic Res
Asunto de la revista:
BIOQUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón