Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China.
Bioengineered. 2022 May;13(5):12760-12771. doi: 10.1080/21655979.2022.2071011.
Previous reports have shown that () infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to infection and VacA. Mice were treated with and VacA, and histopathological analysis of lung tissues was performed using hematoxylin-eosin, Masson's trichrome, and periodic acid Schiff staining. The secretion of inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay. The expression of VacA, nuclear factor-kappa B (NF-κB), and p65 NF-κB was analyzed by Western blotting and immunofluorescence. Cell proliferation and apoptosis were assessed using the MTS assay and flow cytometry, respectively. In mice, infection and VacA treatment promoted the secretion of the inflammatory factors interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-6, and IL-8, increased p65 NF-κB protein phosphorylation, and induced lung injury. Furthermore, infection promoted VacA production. In an cell model, VacA treatment significantly suppressed the proliferation of WI-38 and BEAS-2B cells, promoted apoptosis, induced TNF-α, IL-1β, IL-6, and IL-8 secretion, and promoted p65 NF-κB protein phosphorylation and NF-κB nuclear transfer. The NF-κB inhibitor BAY11-7082 alleviated VacA-induced inflammation and apoptosis and increased cell viability. In conclusion, VacA promotes the secretion of inflammatory factors and induces lung injury through NF-κB signaling.
先前的报告表明，（）感染与呼吸道疾病有关。然而，其发病机制尚不清楚。空泡细胞毒素 A（VacA）是一种主要的外毒素。在本研究中，我们研究了与感染和 VacA 相关的炎症反应的信号通路。用和 VacA 处理小鼠，并用苏木精-伊红、马松三色和过碘酸希夫染色进行肺组织的组织病理学分析。通过酶联免疫吸附试验评估炎症细胞因子的分泌。通过 Western blot 和免疫荧光分析 VacA、核因子-κB（NF-κB）和 p65 NF-κB 的表达。使用 MTS 测定法和流式细胞术分别评估细胞增殖和细胞凋亡。在小鼠中，感染和 VacA 处理促进了促炎因子白细胞介素 1β（IL-1β）、肿瘤坏死因子α（TNF-α）、IL-6 和 IL-8 的分泌，增加了 p65 NF-κB 蛋白磷酸化，并诱导了肺损伤。此外，感染促进了 VacA 的产生。在细胞模型中，VacA 处理显著抑制 WI-38 和 BEAS-2B 细胞的增殖，促进细胞凋亡，诱导 TNF-α、IL-1β、IL-6 和 IL-8 的分泌，并促进 p65 NF-κB 蛋白磷酸化和 NF-κB 核转移。NF-κB 抑制剂 BAY11-7082 减轻了 VacA 诱导的炎症和细胞凋亡，增加了细胞活力。总之，VacA 通过 NF-κB 信号通路促进炎症因子的分泌并诱导肺损伤。
