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Fusobacterium nucleatum triggers proinflammatory cell death via Z-DNA binding protein 1 in apical periodontitis
Cell Communication and Signaling ( IF 8.2 ) Pub Date : 2022-12-20 , DOI: 10.1186/s12964-022-01005-z
Hui Liu 1 , Yuxuan Liu 1 , Wei Fan 1, 2 , Bing Fan 1, 2
Affiliation  

Z-DNA binding protein 1 (ZBP1) is a vital innate immune sensor that regulates inflammation during pathogen invasion. ZBP1 may contribute to pyroptosis, apoptosis and necroptosis in infectious diseases. In this study, Fusobacterium nucleatum (F. nucleatum) infection caused periapical inflammation through proinflammatory cell death and ZBP1 was involved in regulating the inflammatory activities caused by F. nucleatum infection in apical periodontitis (AP). Human periapical tissues were tested by fluorescent in situ hybridization, immunohistochemical staining, immunofluorescence staining, quantitative real-time PCR (qRT‒PCR) and western blotting. F. nucleatum-infected and F. nucleatum extracellular vesicles (F. nucleatum-EVs)-treated RAW264.7 cells were used to detect the expression of inflammatory cytokines and different cell death mechanisms by qRT‒PCR and western blotting. ZBP1 expression in F. nucleatum-infected tissues and RAW264.7 cells was detected by qRT‒PCR, western blotting, and immunohistochemical and immunofluorescence staining. Furthermore, the expression of ZBP1 was inhibited by siRNA and different cell death pathways, including pyroptosis, apoptosis, and necroptosis, and inflammatory cytokines were measured in F. nucleatum-infected RAW264.7 cells. F. nucleatum was detected in AP tissues. F. nucleatum-infected RAW264.7 cells polarized to the M1 phenotype, and this was accompanied by inflammatory cytokine production. High levels of ZBP1 and GSDME (gasdermin E)-mediated pyroptosis, caspase-3-mediated apoptosis and MLKL-mediated necroptosis (PANoptosis) were identified in F. nucleatum-infected tissues and RAW264.7 cells. ZBP1 inhibition reduced inflammatory cytokine secretion and the occurrence of PANoptosis. The present study identified a previously unknown role of ZBP1 in regulating F. nucleatum-induced proinflammatory cell death and inflammatory activation.

中文翻译:

具核梭杆菌通过 Z-DNA 结合蛋白 1 在根尖周炎中引发促炎细胞死亡

Z-DNA 结合蛋白 1 (ZBP1) 是一种重要的先天免疫传感器,可在病原体入侵期间调节炎症。ZBP1 可能导致传染病中的细胞焦亡、细胞凋亡和坏死性凋亡。在这项研究中,具核梭杆菌 (F. nucleatum) 感染通过促炎细胞死亡引起根尖周炎症,ZBP1 参与调节根尖周炎 (AP) 中具核梭杆菌感染引起的炎症活动。通过荧光原位杂交、免疫组织化学染色、免疫荧光染色、定量实时 PCR (qRT-PCR) 和蛋白质印迹检测人根尖周组织。F. nucleatum 感染的和 F. nucleatum 细胞外囊泡(F. nucleatum-EVs)处理的 RAW264。使用 7 个细胞通过 qRT-PCR 和蛋白质印迹检测炎症细胞因子的表达和不同的细胞死亡机制。通过 qRT-PCR、蛋白质印迹、免疫组织化学和免疫荧光染色检测具核梭杆菌感染的组织和 RAW264.7 细胞中的 ZBP1 表达。此外,ZBP1 的表达被 siRNA 和不同的细胞死亡途径抑制,包括细胞焦亡、细胞凋亡和坏死性凋亡,并且在具核梭菌感染的 RAW264.7 细胞中测量了炎性细胞因子。在 AP 组织中检测到 F. nucleatum。F. nucleatum 感染的 RAW264.7 细胞极化为 M1 表型,这伴随着炎症细胞因子的产生。高水平的 ZBP1 和 GSDME (gasdermin E) 介导的细胞焦亡,在 F. nucleatum 感染的组织和 RAW264.7 细胞中发现了 caspase-3 介导的细胞凋亡和 MLKL 介导的坏死性凋亡 (PANoptosis)。ZBP1 抑制减少了炎性细胞因子的分泌和 PANOptosis 的发生。本研究确定了 ZBP1 在调节 F. nucleatum 诱导的促炎细胞死亡和炎症激活中的一个以前未知的作用。
更新日期:2022-12-20
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