The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa.
The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa.
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DOI：
10.1002/path.5990
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发表时间：
2022-10
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先前在人胃癌（GC）和肠上皮化生（IM）组织中发现了衰变加速因子（CD 55）的高水平表达。已经报道了CD 55抑制在癌症中的治疗效果。然而，幽门螺杆菌感染和毒力因子在诱导CD 55中的作用及其与人胃粘膜组织学变化的关系仍不完全清楚。我们假设在感染H. pylori感染，胃粘膜病理改变更明显。来自42 H的胃活检样本的RT-qPCR和免疫组织化学分析。pylori感染者和42例未感染者的胃窦部CD 55 mRNA和蛋白表达均显著升高。pylori感染的患者，这与IM的存在有关，但与萎缩或炎症无关。增加的胃CD 55和IM均与vacA i1型菌株的定殖相关，与cagA状态无关，并且使用vacA的同基因突变体的体外研究证实了VacA诱导胃上皮细胞系中CD 55和sCD 55的能力。siRNA实验研究H. pylori诱导的CD 55显示，胃上皮细胞中的CD 55敲低部分减少了响应于H. pylori，但这不是由于细菌粘附或细胞毒性的调节。最后，通过ELISA分析从相同患者采集的血浆样本中可溶性CD 55（sCD 55）。sCD 55水平不受IM的影响，并且与胃CD 55 mRNA水平无关。这些结果表明，活性vacA i1‐ H型之间存在新的联系。pylori、IM和CD 55，并将CD 55鉴定为在IM管理以及GC治疗中潜在感兴趣的分子。版权所有© 2022作者。病理学杂志由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。
High‐level expression of decay‐accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood. We hypothesised that CD55 would be increased during infection with more virulent strains of H. pylori, and with more marked gastric mucosal pathology. RT‐qPCR and immunohistochemical analyses of gastric biopsy samples from 42 H. pylori‐infected and 42 uninfected patients revealed that CD55 mRNA and protein were significantly higher in the gastric antrum of H. pylori‐infected patients, and this was associated with the presence of IM, but not atrophy, or inflammation. Increased gastric CD55 and IM were both linked with colonisation by vacA i1‐type strains independently of cagA status, and in vitro studies using isogenic mutants of vacA confirmed the ability of VacA to induce CD55 and sCD55 in gastric epithelial cell lines. siRNA experiments to investigate the function of H. pylori‐induced CD55 showed that CD55 knockdown in gastric epithelial cells partially reduced IL‐8 secretion in response to H. pylori, but this was not due to modulation of bacterial adhesion or cytotoxicity. Finally, plasma samples taken from the same patients were analysed for the soluble form of CD55 (sCD55) by ELISA. sCD55 levels were not influenced by IM and did not correlate with gastric CD55 mRNA levels. These results suggest a new link between active vacA i1‐type H. pylori, IM, and CD55, and identify CD55 as a molecule of potential interest in the management of IM as well as GC treatment. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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