Abstract： Objective To investigate Toll-like receptor 2(TLR2)and interleukin-1 receptorassociated kinase 1(IRAK-1)in bacterial lipoprotein(BLP)tolerance.Methods Western blotting was used to confirm the over expression of TLR2 and IRAK-1 in human embryo kidney 293(HEK293)cells.Plasmids for dual luciferase reporter gene with nuclear factor-κB promoter(pNF-κB-Luc)or CMV promoter (phRL-CMV internal control vector)were used to detect the NF-κB activation and the induction of BLP tolerance in HEK-TLR2 cells.Results BLP stimulation resulted in dose-dependent NF-κB activation in HEK293 cells stably expressing TLR2.And BLP pretreatment could reduce NF-κB activation and induce BLP tolerance in HEK-TLR2 cells.The NF-κB activation was 0.329±0.010 and 0.168±0.010 in BLP-activated and BLP-tolerant HEK-TLR2 cells,respectively.After transfection with 0.02μg IRAK-1 plasmid,NF-κB activation in the two groups was 0.493±0.010 and 0.427±0.035,respectively(both P＜0.01).So over expression of IRAK-1 could increase NF-κB activation in a dose-dependent manner.Conclusion These results demonstrated that over expression of IRAK-1 could reverse BLP tolerance,whereas over expression of TLR2 failed to prevent the induction of BLP tolerance.Therefore reduced IRAK-1 protein expression is an important mechanism in the development of BLP-induced tolerance,suggesting that it could be a potentially important target for future therapeutic strategies in bacterial infection and sepsis.