inhibits the cleavage of TRAF1 a CagA-dependent mechanism.

AIM

To study the impact on cleavage of tumor necrosis factor receptor-associated factor 1 (TRAF1) regulated by ().

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 examined using specific caspase inhibitors. The effect of the COOH-terminal TRAF1 fragment on gastric cell apoptosis during infection was measured using flow cytometry. The impact of infection on TRAF1 cleavage was detected in the presence of apoptosis inducer. The roles of virulence factors that may regulate TRAF1 cleavage were analyzed using isogenic and 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 ( < 0.05) as well as promoted -induced cell apoptosis ( < 0.05). infection 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 of and null mutants on the inhibition of TRAF1 cleavage and activation of caspase-8 were significantly attenuated, compared with wild-type , in the presence of the apoptosis inducer, showing that the virulence factor CagA was mainly involved in the inhibition of TRAF1 cleavage.

CONCLUSION

infection significantly inhibits the cleavage of TRAF1 a CagA-dependent mechanism, which would increase the relative amounts of full-length TRAF1 and exert an antiapoptotic effect on -infected cells.