The detrimental eff ect of nitric oxide on tissue is associated with infl ammatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis

Keiji Yasukawa, Hiroto Tokuda, Xin Tun, Hideo Utsumi, Ken Ichi Yamada

研究成果: Contribution to journalArticle査読

47 被引用数 (Scopus)

抄録

Nitric oxide (NO) is thought to be a key molecule in the progression of ulcerative colitis and experimental colitis induced by dextran sodium sulfate (DSS). However, the detrimental eff ect of DSS-induced NO production on the colonic mucosa is incompletely understood. Increases in the expression of adhesion molecules in the vascular endothelium and activated neutrophils (thereby releasing injurious molecules such as reactive oxygen species) are reportedly associated with the pathogenesis of DSS-induced colitis. We investigated if the detrimental eff ect of NO production on the colonic mucosa was attributable to the activation of neutrophil infi ltration by NO in mice with DSS-induced colitis. NO2-/NO3- content in the middle and distal colon was increased on days 5 and 7, but alterations in the proximal colon were not observed. Myeloperoxidase (MPO) activity and expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) were signifi cantly increased in the entire colon, whereas TNF-α levels were signifi cantly increased only in the middle and distal colon on day 7. The pathology of colitis and increases in colonic MPO activity, P-selectin, ICAM-1, and TNF-α levels were suppressed by the inducible NO synthase (iNOS)-specifi c inhibitor aminoguanidine and NO scavenger c-PTIO, whereas all but TNF-α levels were increased by the non-specifi c NOS inhibitor L-NAME. These fi ndings suggest that iNOS-derived NO increases TNF-α levels in the middle and distal colon and increased TNF-α levels induce expression of P-selectin and ICAM-1, thereby promoting the infi ltration of activated neutrophils, which leads to damage to colonic tissue.

本文言語英語
ページ(範囲)1427-1436
ページ数10
ジャーナルFree Radical Research
46
12
DOI
出版ステータス出版済み - 12 2012

All Science Journal Classification (ASJC) codes

  • 生化学

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