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  • Title: [Role of the activation of interleukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury].
    Author: Chen LP, Qian YY, Cai M, Li ZL, Bai HW, Shi BY.
    Journal: Zhonghua Wai Ke Za Zhi; 2009 Jun 01; 47(11):863-7. PubMed ID: 19961020.
    Abstract:
    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.
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