[Influence on the cytokines expression on hepatic tissue by inhibition the signal pathway of inflammatory mediators following extensive hepatectomy in rats].
OBJECTIVE
To investigate the impact of AG490, a cytokine signaling inhibitor, on cytokine signaling pathway with phosphorylation levels of Janus kinase 2 (Jak2) and singal transducers and activators of transcription 3 (Stat3), and liver pro-/anti-inflammatory cytokine expressions.


METHODS
Rats were divided into two groups after surgery: control group, without treatment; AG490 group, with AG490 (1 mg.kg(-1).12 h(-1)) administration intraperitoneally, immediately and through 36 hs after the operation. Western blotting was used to detect the levels of phosphorylated Jak2 and Stat3. Semi-quantitative RT-PCR was employed to examine Interleukin-6 (IL-6) and Interleukin-10 (IL-10) expression.


RESULTS
At 8 h and 12 h post-operatively, the phosphorylation levels of Jak2 and Stat3 were significantly inhibited in the AG490 group when compared with the control group. The DNA levels of IL-6 in the liver of the AG490 group rat at the same time points were also decreased, whereas IL-10 levels markedly increased. These changes made the ratio of IL-6/IL-10 dropped significantly.


CONCLUSIONS
AG490 ameliorates the overwhelming inflammatory response via a mechanism of blocking cytokine signaling transduction and consequently suppresses the ratio of pro-/anti-inflammatory cytokine expression, which exerts potential clinical implications of use of anti-inflammatory agents in hepatic surgery.
Mao
Yi-lei
YL
Liver Surgery Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. maoy@public3.bta.net.cn
Yu
Zhuo
Z
Sang
Xin-ting
XT
Lu
Xing
X
Yang
Zhi-ying
ZY
Zhong
Shou-xian
SX
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D053614:Janus Kinase 2; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2