[The influence of over expression of interleukin-1 receptor-associated kinase 1 on bacterial lipoprotein-induced tolerance].
OBJECTIVE
To investigate Toll-like receptor 2 (TLR2) and interleukin-1 receptor-associated 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-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.


RESULTS
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 P<0.01). So over expression of IRAK-1 could increase NF-KappaB activation in a dose-dependent manner.


CONCLUSIONS
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.
Li
Chong-Hui
CH
Hepatobiliary Surgery Institute, PLA General Hospital, Beijing 100853, China. Lichonghui720@yahoo.com.cn
Wang
Jin-Jing
JJ
Gao
Li-Jie
LJ
Wang
Jiang-Huai
JH
Huang
Zhi-Qiang
ZQ
D057809:HEK293 Cells; D006801:Humans; D007108:Immune Tolerance; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology / Q000378:metabolism*; D008074:Lipoproteins / Q000276:immunology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*
D008074:Lipoproteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases