title: Cytoprotective effects of human interleukin-10 gene transfer against necrosis and apoptosis induced by hepatic cold ischemia/reperfusion injury.
abstract: BACKGROUND
  Apoptosis as well as necrosis may play an important role in hepatic ischemia/reperfusion (I/R) injury. Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. The study focused on cytoprotective and antiapoptotic pathways to assess mechanisms by which gene transduction of human IL-10 (hIL-10) may renders grafts resistant to the cold I/R injury.
  
  
  METHODS
  Adenoviruses encoding hIL-10 or beta-galactosidase (LacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48h after transduction, and stored for 12h at 4 degrees C lactated Ringer's solution prior to being transplanted. Graft survival, liver function, the degree of necrosis and apoptosis, and the molecules of apoptotic networks were assessed.
  
  
  RESULTS
  Ad-hIL-10 pretreatment significantly prolonged the survival of liver grafts by improving liver function, preserving hepatocyte integrity and architecture, and depressing intrahepatic apoptosis and necrosis. In addition, Ad-hIL-10 pretreatment diminished the release of cytochrome c from mitochondria into cytoplasm and caspase-3 activity, with simultaneous up-regulated of antioxidant HO-1 and anti-antiapoptotic Bcl-2 molecules.
  
  
  CONCLUSIONS
  Adenoviral gene transfer of hIL-10 ameliorated cold I/R injury by decreasing hepatic necrosis and apoptosis. The underlying mechanism of cytoprotective effects may at least be involved with the inhibition of caspase-3 activity and mitochondrial cytochrome c release, and the up-regulation of antiapoptotic (Bcl-2) and antioxidant (HO-1) molecules.
authors: Department of Organ Transplantation, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors: Jie-qun
authors: JQ
authors: Li
authors: Hai-zhi
authors: HZ
authors: Qi
authors: Zhi-jun
authors: ZJ
authors: He
authors: Wei
authors: W
authors: Hu
authors: Zhong-zhou
authors: ZZ
authors: Si
authors: Yi-ning
authors: YN
authors: Li
authors: Dong-bo
authors: DB
authors: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003080:Cold Temperature; D003451:Cryoprotective Agents; D045304:Cytochromes c / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival / Q000502:physiology; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D016031:Liver Transplantation; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D003451:Cryoprotective Agents; C508609:IL10 protein, human; D016753:Interleukin-10; D045304:Cytochromes c