幽門桿菌已知是胃部的病源菌，在世界上的感染的盛行率超過50％。之前的研究指出，幽門桿菌的感染和一些腸胃疾病有密切的相關性，包括慢性胃部發炎、胃潰瘍、十二指腸潰瘍、胃黏膜性淋巴腫瘤及胃上皮細胞瘤。幽門桿菌感染會持續性的吸引嗜中性球、單核球的浸潤而導致胃部持續性的發炎。幽門桿菌引起胃部的發炎反應中有些特定的細胞激素會參與其中，包含腫瘤壞死因子、IL-1beta等。先前實驗室的研究指出中性球浸潤的急性胃發炎指數及較高的胃潰瘍發生率和宿主腫瘤壞死因子啟動子上單一核甘酸多型性有相關性。因此，本篇研究主要在於探討幽門桿菌誘發胃上皮細胞表現腫瘤壞死因子的機制。我們的結果證實了幾點，(1)幽門桿菌誘發胃上皮細胞表現腫瘤壞死因子的調控是在轉錄層級。(2)幽門桿菌的感染可以使NF-kB p65磷酸化，而活化後的NF-kB p65可以結合上腫瘤壞死因子啟動子上NF-kB1、NF-kB2結合序列來影響腫瘤壞死因子啟動子的活性。(3)幽門桿菌感染胃上皮細胞可以活化MAPK/ERK1/2、MAPK/p38兩條訊息傳遞路徑。(4)幽門桿菌的CagA蛋白參與在幽門桿菌活化ERK1/2、p38訊息傳遞路徑上。但是，CagA蛋白只少許的參與在活化腫瘤壞死因子蛋白的表現。(5)三種幽門桿菌致病因子CagA、VacA、BabA都有參與在幽門桿菌活化腫瘤壞死因子啟動子活性的調控中。(6)幽門桿菌活化胃上皮細胞表現腫瘤壞死因子的調控機制是經過多重步驟及複雜的訊息傳遞路徑的。

Helicobacter pylori has been well known as an important gastric pathogen with worldwide prevalence of infection near 50%. The previous reports revealed infection of H. pylori can be closely related with variable gastro-duodenal diseases, including chronic gastritis, gastric ulcer, duodenal ulcer, mucosa-associated lymphoid tissue lymphoma (MALToma) and even gastric adenocarinoma. The continuous inflammation of stomach should be caused by H. pylori–induced infiltration of neutrophil and mononuclear cell. The gastritis of H. pylori-induced should be mediated with certain cytokine cascades, including TNF-, IL-1B, and etc. Our previous report disclosed the infiltration of neutrophil index to represent the acute inflammation severity and a higher gastric ulcer rate are related with the hosts’ single nucleotide polymorphisms of TNF- promoter. Therefore, this study aimed to elucidate the mechanisms of H. pylori-induced TNF- expression in the gastric epithelial cell line. Our results showed the following evidence, including (1) Induction of TNF- expression in gastric epithelial cell by H. pylori is regulated at transcriptional level; (2) H. pylori induces phosphorylation of NF-kB p65. Phosphor-NF-kB p65 induces TNF-promoter activity through binding to NF-kB2 binding sequence of TNF- promoter. (3) Phosphorylation of ERK1/2, p38 in the gastric epithelial cell line are induced by H. pylori infection. (4) CagA protein is involved in H. pylori activated ERK1/2, p38 signaling transductional pathways in MKN45 cell. CagA slightly involve in expression of H. pylori induced TNF-. (5) Three virulence factors as CagA, VacA and BabA are all involved in the mechanisms of H. pylori induced TNF- promoter activity. (6) Mechanisms of H. pylori induced TNF- promoter activity is going through a multiple steps and complex signaling through the transductional pathways.

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