[Role of the activation of interleukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury].
OBJECTIVE
To investigate the role of IL-6/STAT3 pathway in the proliferation of cholangiocyte induced by cold ischemia and reperfusion injury.


METHODS
Rats 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.


RESULTS
Minimal 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.


CONCLUSIONS
IL-6/STAT3 pathway might participate to initiate cholangiocytes regeneration after cold ischemia and preservation injury, which might benefit biliary recovery after liver transplantation.
Chen
Li-Ping
LP
Organ Transplantation Center, Second Affiliated Hospital, Chinese People's Liberation Army General Hospital, Beijing 100091, China.
Qian
Ye-Yong
YY
Cai
Ming
M
Li
Zhou-Li
ZL
Bai
Hong-Wei
HW
Shi
Bing-Yi
BY
D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D049109:Cell Proliferation; D050377:Cold Ischemia; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat