title: Chronic graft dysfunction and improvement by cytokine response modifier a protein transfection.
abstract: OBJECTIVE
  Cytokine response modifier A protein is a caspase inhibitor that inhibits caspase activity and protects cells from apoptosis. Chronic cyclosporine nephropathy is a significant cause of chronic graft dysfunction. We explored cytokine response modifier A protein-alleviated chronic cyclosporine nephropathy for ways of improving chronic graft dysfunction.
  
  
  METHODS
  Cytokine response modifier A protein-transferring HK-2 cells were cultured with different concentrations of cyclosporine. Cytokine response modifier A protein mRNA and proteins were detected by real-time polymerase chain reaction and Western blot, cell viability was detected by (3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide), and apoptosis was detected by flow cytometry.
  
  
  RESULTS
  Cyclosporine caused a concentration-dependent and time-dependent loss of cell viability in HK-2 cells. Cytokine response modifier A protein mRNA was expressed at 48 and 72 hours (P < .05), while protein was detected at 72 hours. Cell viability in the cytokine response modifier A protein-transfected group was significantly greater than that of the control group when treated with 1 µg/mL, 10 µg/mL, or 20 µg/mL cyclosporine at 24 or 48 hours (P < .05). The apoptosis in cytokine response modifier A protein-transfected cells was significantly lower than that of controls (P < .05).
  
  
  CONCLUSIONS
  Cytokine response modifier A protein protects renal cells from cyclosporine injury by inhibiting activated caspases. Cytokine response modifier A protein transfection may improve chronic cyclosporine nephropathy and provide for improving chronic graft dysfunction.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Ministry Health of China, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.forename: Chengwen
authors.initials: C
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015843:Serpins; D014764:Viral Proteins; D016572:Cyclosporine; C074641:interleukin-1beta-converting enzyme inhibitor