Mechanisms of Helicobacter pylori virulence factor CagA in promoting inflammatory response by targeting SHARPIN
10.13431/j.cnki.immunol.j.20230121
- VernacularTitle:幽门螺杆菌毒力因子CagA通过靶向SHARPIN促进炎症反应的机制研究
- Author:
Nayun SU
1
;
Tingyi WANG
;
Qianfei ZUO
;
Qian LU
;
Zhe ZHAO
;
Hao MEI
;
Bin WANG
;
Dongfeng CHEN
;
Chunhui LAN
Author Information
1. 400042 重庆,陆军军医大学陆军特色医学中心(大坪医院)消化内科消化系统肿瘤精准防治重庆市重点实验室
- Keywords:
Helicobacter pylori;
CagA;
Inflammation
- From:
Immunological Journal
2023;39(12):1021-1027
- CountryChina
- Language:Chinese
-
Abstract:
Chronic inflammation induced by Helicobacter pylori is considered to be one of the main causes of gastric cancer,and CagA is a main virulence factor of H.pylori.The study aimed to investigate the role and mechanism of CagA in host inflammatory response.Mass spectrometry was used to identify the interacting proteins of CagA in AGS cells.By immunoprecipitation and immunofluorescence,the interaction was validated.Pathway expression was detected by immunoblotting after knockdown by using siRNA,and mRNA levels of inflammatory cytokines were detected by quantitative PCR.CagA-induced inflammatory responses were detected in clinical samples using hemoglobin-eosin staining(H&E).Data showed that CagA interacted with SHARPIN.And CagA activated the NF-κB signaling pathway and upregulated the mRNA and protein levels of the inflammatory cytokines IL-6,IL-8,and TNF-α,as compared with the CagA knockout strain(all P<0.05).Knockdown of SHARPIN by siRNA reduced inflammation levels and partially inhibit NF-κB signaling.In clinical samples,CagA-positive samples exhibited stronger inflammatory responses.To sum up,CagA promoted the host inflammatory response,and CagA-induced inflammatory response was reduced when SHARPIN was partially inhibited,suggesting that CagA activates the NF-κB signaling pathway through binding to SHARPIN.
