title: Helicobacter pyloriinhibits the cleavage of TRAF1viaa CagA-dependent mechanism.
abstract: OBJECTIVE
  To study the impact on cleavage of tumor necrosis factor receptor-associated factor 1 (TRAF1) regulated byHelicobacter pylori(H. pylori).
  
  
  METHODS
  Cleavage of TRAF1 was detected by western blotting in the human gastric cancer cell line AGS following treatment with an apoptosis inducer. Cleavage of TRAF1 mediated by caspase was examinedin vitrousing specific caspase inhibitors. The effect of the COOH-terminal TRAF1 fragment on gastric cell apoptosis duringH. pyloriinfection was measured using flow cytometry. The impact ofH. pyloriinfection on TRAF1 cleavage was detected in the presence of apoptosis inducer. The roles ofH. pylorivirulence factors that may regulate TRAF1 cleavage were analyzed using isogeniccagA-, vacA-andcagE-null mutants.
  
  
  RESULTS
  TRAF1 was found to be cleaved in AGS cells treated with the apoptosis inducer, and caspase-8 was the major caspase involved in the cleavage of TRAF1. The COOH-terminal TRAF1 fragment significantly induced cell apoptosis (P< 0.05) as well as promotedH. pylori-induced cell apoptosis (P< 0.05).H. pyloriinfection was found to significantly inhibit the cleavage of TRAF1 and to inhibit the activation of caspase-8 in the presence of the apoptosis inducer at specific infection times and different cell/bacteria ratios. We also found that the effects ofcagE-andcagA-null mutants on the inhibition of TRAF1 cleavage and activation of caspase-8 were significantly attenuated, compared with wild-typeH. pylori, in the presence of the apoptosis inducer, showing that the virulence factor CagA was mainly involved in the inhibition of TRAF1 cleavage.
  
  
  CONCLUSIONS
  H. pyloriinfection significantly inhibits the cleavage of TRAF1viaa CagA-dependent mechanism, which would increase the relative amounts of full-length TRAF1 and exert an antiapoptotic effect onH. pylori-infected cells.
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Xiu-Kun
authors.initials: XK
authors.lastname: Wan
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Sheng-Ling
authors.initials: SL
authors.lastname: Yuan
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Hao-Xia
authors.initials: HX
authors.lastname: Tao
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Zhang-Yan
authors.initials: ZY
authors.lastname: Guan
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: Xiu-Kun Wan, Sheng-Ling Yuan, Yan-Chun Wang, Hao-Xia Tao, Wei Jiang, Zhang-Yan Guan, Cheng Cao, Chun-Jie Liu, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Chun-Jie
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D009154:Mutation; D013270:Stomach; D013274:Stomach Neoplasms / Q000382:microbiology; D047990:TNF Receptor-Associated Factor 1 / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D047990:TNF Receptor-Associated Factor 1; C074689:VacA protein, Helicobacter pylori; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori; D003513:Cycloheximide; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: Apoptosis; CagA; Cleavage; Helicobacter pylori; Tumor necrosis factor receptor-associated factor 1