title: Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation.
abstract: BACKGROUND
  The role of inducible costimulator (ICOS) in transplantation immunity remains unclear.
  
  
  METHODS
  A Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-gamma and tumor-necrosis factor-alpha levels were determined.
  
  
  RESULTS
  Recipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-gamma and tumor-necrosis factor-alpha, suppress cell infiltration into grafts, and promote tolerance in the interference group.
  
  
  CONCLUSIONS
  Our data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect allografts from acute rejection.
authors.affiliation: Department of Hepatobliliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Haizhong
authors.initials: H
authors.lastname: Liu
authors.forename: Zuojin
authors.initials: Z
authors.lastname: Liu
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Feiwu
authors.initials: F
authors.lastname: Long
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.forename: Lünan
authors.initials: L
authors.lastname: Yan
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D015153:Blotting, Western; D015536:Down-Regulation; D006084:Graft Rejection / Q000517:prevention & control*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000097:blood; D008055:Lipids; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008853:Microscopy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C556695:Icos protein, rat; D007202:Indicators and Reagents; D060889:Inducible T-Cell Co-Stimulator Protein; D008055:Lipids; C086724:Lipofectamine; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma