[The influence of over expression of interleukin-1 receptor-associated kinase 1 on bacterial lipoprotein-induced tolerance]

To investigate Toll-like receptor 2 (TLR2) and interleukin-1 receptor-associated kinase 1 (IRAK-1) in bacterial lipoprotein (BLP) tolerance.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-KappaB promoter (pNF-KappaB-Luc) or CMV promoter (phRL-CMV internal control vector) were used to detect the NF-KappaB activation and the induction of BLP tolerance in HEK-TLR2 cells.BLP stimulation resulted in dose-dependent NF-KappaB activation in HEK293 cells stably expressing TLR2. And BLP pretreatment could reduce NF-KappaB activation and induce BLP tolerance in HEK-TLR2 cells. The NF-KappaB activation was 0.329+/-0.010 and 0.168+/-0.010 in BLP-activated and BLP-tolerant HEK-TLR2 cells, respectively. After transfection with 0.02 microg IRAK-1 plasmid, NF-KappaB activation in the two groups was 0.493+/-0.010 and 0.427+/-0.035, respectively (both P0.01). So over expression of IRAK-1 could increase NF-KappaB activation in a dose-dependent manner.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.