title: IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling Pathway in Mice.
abstract: BACKGROUND
  The protective role of IL-11, an IL-6 family cytokine, has been implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its role has not been elucidated in liver IRI. This study was designed to evaluate the effects of IL-11 and its mechanism of action on liver IRI in a mouse model.
  
  
  METHODS
  A partial (70%) warm liver IRI was induced by interrupting the artery/portal vein blood supply to the left/middle liver lobes. IL-11 mRNA expression of ischemic liver after reperfusion was analyzed. Signal transducer and activator of transcription 3 (STAT3) was analyzed following IL-11 treatment in vivo and in vitro. Next, IL-11 was injected intraperitoneally (ip) 1 hour before ischemia. Liver injury was assessed based on serum alanine aminotransferase levels and histopathology. Apoptosis and inflammation were also determined in the ischemic liver. To analyze the role of STAT3 in IL-11 treatment, STAT3 siRNA or non-specific (NS) siRNA was used in vitro and in vivo.
  
  
  RESULTS
  IL-11 mRNA expression was significantly increased after reperfusion in the ischemic liver. STAT3, as a target of IL-11, was activated in hepatocytes after IL-11 treatment in vivo and in vitro. Next, effects of IL-11/STAT3 signaling pathway were assessed in liver IRI, which showed IL-11 treatment significantly attenuated liver IRI, as evidenced by reduced hepatocellular function and hepatocellular necrosis/apoptosis. In addition, IL-11 treatment significantly inhibited the gene expressions of pro-inflammatory cytokines (TNF-α and IL-10) and chemokines (IP-10 and MCP-1). To determine the role of STAT3 in the hepatoprotective effects of IL-11, STAT3 siRNA or NS siRNA was used prior to IL-11 treatment. The results showed STAT3 knockdown abrogated the protective effects of IL-11 in vitro and in vivo.
  
  
  CONCLUSIONS
  This work provides first-time evidence for the protective effect of IL-11 treatment on hepatocyte in liver IRI, through the activation of the STAT3 pathway.
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Yixing People's Hospital, 75 Tongzhenguan Road, Yixing, Jiangsu Province, P. R China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Weisu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Xuequan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Surgical Oncology, Affiliated Hospital of Nanjing University of TCM, 155 Hanzhong Road, Nanjing, Jiangsu Province, P. R China.
authors.forename: Fukun
authors.initials: F
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D004789:Enzyme Activation; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D017370:Interleukin-11 / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D015427:Reperfusion Injury / Q000188:drug therapy*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C556062:IL10 protein, mouse; D017370:Interleukin-11; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000410:Alanine Transaminase