Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease
Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease
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DOI：
10.1016/s0016-5085(96)70055-0
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发表时间：
1996-10-01
期刊：
影响因子：
29.4
通讯作者：
Stenson, WF
中科院分区：
文献类型：
--
作者：
Singer, II;Kawka, DW;Stenson, WF
背景与目的：诱导型一氧化氮合酶(INOS)在脂多糖或细胞因子作用下在多种细胞中产生。早期的研究表明，溃疡性结肠炎与iNOS产生的NO增加有关；然而，NO合成的细胞来源尚未确定。NO诱导细胞损伤的一个可能机制是通过与超氧化物相互作用产生过氧亚硝酸盐，过氧亚硝酸盐与酪氨酸反应形成细胞蛋白质中的硝基酪氨酸。方法：用新型单特异性人iNOS抗体(NO-53)免疫组织化学染色，观察正常人、溃疡性结肠炎、克罗恩病和憩室炎结肠黏膜中iNOS和硝基酪氨酸的细胞分布。结果：iNOS在溃疡性结肠炎、克罗恩病和憩室炎的炎性上皮细胞中有较强的表达，而在未发炎的结肠上皮细胞中未检测到iNOS的表达。在炎症的结肠上皮中也观察到了硝基酪氨酸的标记，并与附近的iNOS染色有关；在正常的粘膜上皮中未检测到硝基酪氨酸。固有层、单核细胞和中性粒细胞也有iNOS和硝基酪氨酸的表达。结论：iNOS在炎症的人结肠上皮细胞中被诱导，并与过氧亚硝酸盐的形成和细胞内蛋白质的硝化有关。
Background & Aims: Inducible nitric oxide synthase (iNOS) is generated in several cell types by treatment with lipopolysaccharides or cytokines. Earlier studies suggested that ulcerative colitis is associated with increased NO produced by iNOS; however, the cellular source of the NO synthesis was not identified. A possible mechanism of NO-induced cellular damage is through its interaction with superoxide to produce peroxynitrite, which reacts with tyrosine to form nitrotyrosine in cellular proteins. Methods: Using immunoperoxidase microscopy with a new monospecific human iNOS antibody (NO-53), the cellular distribution of iNOS and nitrotyrosine was examined using human colonic mucosa from normal bower, ulcerative colitis, Crohn's disease, and diverticulitis. Results: Intense focal iNOS labeling was localized to the inflamed colonic epithelium in ulcerative colitis, Crohn's disease, and diverticulitis but was not detectable in the uninflamed epithelium. Nitrotyrosine labeling was also observed in the inflamed colonic epithelium and was associated with nearby iNOS staining; nitrotyrosine was undetectable in normal mucosal epithelium. iNOS and nitrotyrosine were also detected in lamina propria mononuclear cells and neutrophils. Conclusions: these findings suggest that iNOS is induced in the inflamed human colonic epithelium and is associated with the formation of peroxynitrite and the nitration of cellular proteins.