Yeh Jia-Yin, Lin Hwai-Jeng, Kuo Chia-Jung, Feng Chun-Lung, Chou Chia-Huei, Lin Chia-Der, Wu Hui-Yu, Li Chen-Yi, Chiu Cheng-Hsun, Lai Chih-Ho
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei, Taiwan.
Front Cell Dev Biol. 2021 Feb 23;8:617419. doi: 10.3389/fcell.2020.617419. eCollection 2020.
infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to -associated disease progression. The cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by VacA. Furthermore, rCdtC reduces CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for cytotoxin actions lipid rafts, ameliorating -induced pathogenesis.
感染与多种胃肠道疾病相关，包括胃炎、消化性溃疡和胃肠道腺癌。两种主要的细胞毒素，即空泡毒素A（VacA）和细胞毒素相关基因A（CagA），与脂筏密切相互作用，促进相关疾病进展。细胞致死性膨胀毒素由三个亚基组成：CdtA、CdtB和CdtC。其中，CdtA和CdtC与膜脂筏结合，这对于CdtB进入细胞至关重要。在本研究中，我们使用重组CdtC（rCdtC）来拮抗细胞毒素在细胞中的功能。我们的结果表明，rCdtC减轻了VacA诱导的细胞空泡化。此外，rCdtC减少了CagA易位，这降低了核因子κB激活和白细胞介素-8的产生，从而减轻了胃上皮细胞炎症。这些结果表明，CdtC劫持胆固醇以竞争细胞毒素在脂筏中的作用，改善相关诱导的发病机制。
