Physiological action of nitric oxide produced by a stimulation of endotoxin from Helicobacter pylori on gastric mucosa

幽门螺杆菌内毒素刺激产生一氧化氮对胃粘膜的生理作用

基本信息

批准号：
15590087
负责人：
YOSHIMURA Tetsuhiko
金额：
$ 2.3万
依托单位：
Yamagata Promotional Organization for Industrial Technology (2004)Yamagata Public Corporation For the Development Of Industry, Institute Life Support Technology (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Helicobacter pylori, a gram-negative bacterium, is the primary cause of gastritis and a major contributor to peptic ulcer disease. Despite its importance as a human pathogen, principal factor of pathogenicity of the bacterium remains to be identified Nitric oxide (NO) released due to the induction of Ca^<2+> independent isoform of nitric oxide synthase (iNOS) by lipopolysaocharide or endotoxin from a gram-negative bacterium bas been known to be deleterious to a gastric mucosa. In the present shady, to elucidate the physiological action of H.pylori LPS on gastric mucosa and the role of NO, we were carried out both in vivo and in vitro study by employing E.coli LPS as a control.1. IT pylori LPS was isolated from gram-order bacteria by the phenol-water extraction method, and then further purified by tine enzymatic digestion of RNA, DNA, and proteins.2. In vitro cross talk between products from iNOS and cyclooxygenase (COX) in the rat gastric mucosa during endotoxemia was examined in vivo. The results demonstrate that in the E cob LPS-treated rat gastric mucosa, PGE2, a COX product, enhances after activation of iNOS. The effect of COX activity on iNOS-NO pathway is important in the regulation of gastric mucosal integrity inflammatory states.3. We further elucidated the interaction of LPS with gastric epithelial cells by using a normal mouse gastric surface mucous cell line (GSM06). Our findings suggest that both LPSs from H.pylori and E.coli induce the iNOS and Toll-like receptor (TLR) 2 through the TLR 4 expressed constitutively in GSM06. This mechanism on TLR 2 induction can be crucial for maintenance of gastric mucosal integrity.

幽门螺杆菌是一种革兰氏阴性细菌，是胃炎的主要原因，也是导致消化性溃疡疾病的主要原因。尽管它是人类病原体的重要性，但由于脂肪polyyacary（Inos）诱导了Ca^<2+>独立的同工型，脂肪酸酸酯（Inos）被脂肪酸糖浆或内托毒素诱导Ca^<2+>独立的同工型而释放的一氧化氮（NO）仍有待鉴定。在目前的阴影中，为了阐明幽门螺杆菌LPS对胃粘膜的生理作用和NO的作用，我们通过使用E.Coli LPS作为对照1进行了体内和体外研究。通过苯酚萃取方法从革兰氏阴性细菌中分离出IT幽门lps，然后通过RNA，DNA和蛋白质的Tine酶消化进一步纯化。2。在体内检查了大鼠胃粘膜中iNOS和环氧合酶（COX）产品之间的体外交叉聊天。结果表明，在E COB LPS处理的大鼠胃粘膜PGE2中，Cox产品在激活INOS后增强。 Cox活性对INOS-NO途径的影响在调节胃粘膜完整性炎症状态下很重要3。我们通过使用正常的小鼠胃表面粘液细胞系（GSM06）进一步阐明了LPS与胃皮细胞的相互作用。我们的发现表明，来自H. pylori和E.coli的LPS通过TLR 4在GSM06中构成表达的TLR 4诱导Inos和Toll样受体（TLR）2。 TLR 2诱导的这种机制对于维持胃粘膜完整性至关重要。