Influence on the cytokines expression on hepatic tissue by inhibition the signal pathway of inflammatory mediators following extensive hepatectomy in rats.
- Author:
Yi-lei MAO
1
;
Zhuo YU
;
Xin-ting SANG
;
Xing LU
;
Zhi-ying YANG
;
Shou-xian ZHONG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cytokines; biosynthesis; DNA-Binding Proteins; metabolism; Hepatectomy; methods; Interleukin-10; biosynthesis; Interleukin-6; biosynthesis; Janus Kinase 2; Liver; drug effects; physiology; Male; Protein-Tyrosine Kinases; metabolism; Proto-Oncogene Proteins; metabolism; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; Signal Transduction; drug effects; physiology; Trans-Activators; metabolism; Tyrphostins; pharmacology
- From: Chinese Journal of Surgery 2005;43(1):6-9
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSRats 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.
RESULTSAt 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.
CONCLUSIONSAG490 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.
