Role of the activation of interleukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury.
- Author:
Li-Ping CHEN
1
;
Ye-Yong QIAN
;
Ming CAI
;
Zhou-Li LI
;
Hong-Wei BAI
;
Bing-Yi SHI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Bile Ducts, Intrahepatic; pathology; Cell Proliferation; Cold Ischemia; Disease Models, Animal; Epithelial Cells; pathology; Interleukin-6; metabolism; Liver; metabolism; pathology; Liver Transplantation; Male; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; metabolism; pathology; STAT3 Transcription Factor; metabolism
- From: Chinese Journal of Surgery 2009;47(11):863-867
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of IL-6/STAT3 pathway in the proliferation of cholangiocyte induced by cold ischemia and reperfusion injury.
METHODSRats were randomized into CP 1 h and CP 12 h groups (supplied livers were preserved for 1 or 12 h), anti-IL-6R (rats in CP 12 h group were administrated with anti-rat soluble IL-6 receptor antibody), and control group. At 1, 3, 7, 14 d postoperative, IL-6 concentration in liver homogenate and cholangiocyte proliferation were detected by enzyme linked immunosorbent assay and histochemistry respectively. Expressions of IL-6 mRNA, phosphorylated-STAT3 and cyclin D1 protein in cholangiocytes were determined by real-time PCR or Western blot analysis. Serum concentrations of ALP and GGT and histology analysis were also performed.
RESULTSMinimal expressions of IL-6, p-STAT3 and cyclin D1 were detected in CP 1 h group, with a slight cholangiocytes proliferation. Cholangiocytes responded to extended cold preservation with severe bile duct injures and marked increase in IL-6 secretion, p-STAT3 and cyclin D1 protein expression, followed by compensatory cholangiocytes regeneration. Parallel to this observation, biochemical index and morphology indicated that bile duct injury was recovery at 14 d postoperative. However, anti-sIL-6R inhibited cholangiocytes proliferation and reduced the expressions of IL-6, STAT3 and cyclin D, with the cellular injury and increase of serum ALP or GGT.
CONCLUSIONSIL-6/STAT3 pathway might participate to initiate cholangiocytes regeneration after cold ischemia and preservation injury, which might benefit biliary recovery after liver transplantation.