Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection.
Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection.
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DOI：
10.1155/2013/248585
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kao JY
中科院分区：
文献类型：
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作者：
Yang JC;Yang HC;Shun CT;Wang TH;Chien CT;Kao JY
免疫细胞中的炎症小体/caspase-1信号通路在细菌发病机制中发挥着关键作用；然而，幽门螺杆菌感染期间胃上皮中这一途径的调节尚未阐明。在这里，我们研究了儿茶素 (CA)、唾液酸 (SA) 或 CA 和 SA 的组合 (CASA) 对幽门螺杆菌诱导的 caspase-1 介导的上皮损伤以及体外（AGS 细胞）和体内（BALB/c 小鼠）幽门螺杆菌定植的影响。我们的结果表明，在幽门螺杆菌感染的AGS细胞中，caspase-1的活性及其下游底物IL-1β的表达上调。此外，我们观察到幽门螺杆菌感染小鼠胃粘膜的氧化应激、NADPH 氧化酶 gp91phox、CD68、caspase-1/IL-1β 和细胞凋亡增加，但自噬减少。我们进一步证明，CASA 治疗可产生协同抗 H.幽门螺杆菌活性，比单独使用 CA 或 SA 治疗更有效。特别是，用 CASA 治疗 10 天，高达 95% 的幽门螺杆菌感染小鼠消除了幽门螺杆菌感染。综上所述，我们认为幽门螺杆菌的发病机制涉及胃上皮炎症小体/caspase-1信号通路，我们的结果表明CASA能够减弱该通路并有效根除幽门螺杆菌感染。
The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells) and in vivo (BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection.