[The experimental study on the expression of toll-like receptor 2 in fulminant hepatic failure].
OBJECTIVE
In order to explore the role of toll-like receptors 2 (TLR2) in initiating inflammatory response, the expression of TLR2 of the liver and IL-18, TNF-alpha and IFN-gamma of plasma in fulminant hepatic failure was analysed.


METHODS
D-galactosamine (D-Gal, 900 mg/kg) and lipopolysaccharide (LPS, 10 microg/kg) were administered intraperitoneally into the BALB/C mice. To evaluate the hepatic injury, serum transaminase (ALT and AST) and plasma IL-18, TNF-alpha and IFN-gamma were determined and the mortality was observed at various time points following the intraperitoneal injection. The level of TLR2 mRNA was measured by semiquantitative RT-PCR. The protein expression of TLR2 in the liver was detected by immunohistochemistry. The data was analyzed by SAS software.


RESULTS
After 4 hours of intraperitoneal injection of D-Gal/LPS, the serum transaminase and plasma IL-18, TNF-alpha and IFN-gamma levels were elevated. The treated mice began to die at 7 hours. The mortality reached up to 80% at 10 h. TLR2 mRNA was expressed at a low level in liver tissues of normal mice, while it was significantly increased and maintained at a higher level following intraperitoneal injection with D-Gal/LPS. The expression of TLR2 protein was similar to that of the TLR2 mRNA, and the expression of TLR2 mRNA was positively correlated with the concentration of plasma IL-18, TNF-alpha and IFN-gamma (r=0.36, P=0.02; r = 0.48, P 0.003; r = 0.72, P<0.001) at different time points.


CONCLUSIONS
Our results showed that TLR2 was involved in initiating and inducing the expression of proinflammation cytokines in this model of fulminant hepatic failure. The results suggest that adjusting the expression of TLR2 might be a new strategy in preventing the development of infectious diseases
Yan
Chun-Gen
CG
Department of Infectious Diseases, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Xie
Qing
Q
Zhou
Xia-Qiu
XQ
Xu
Yu-Min
YM
Yu
Hong
H
Guo
Qing
Q
D000818:Animals; D005688:Galactosamine; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D007371:Interferon-gamma