title: Knockdown of microRNA-155 in Kupffer cells results in immunosuppressive effects and prolongs survival of mouse liver allografts.
abstract: BACKGROUND
  Our previous studies have shown that Kupffer cells (KCs) play a crucial role in postoperative pathologic changes. Recent reports have demonstrated that microRNA-155 (miR-155) is associated with inflammation and upregulation of proinflammatory mediators in the peripheral blood and allografts of transplant patients. However, the precise mechanism for this remains unknown.
  
  
  METHODS
  KCs isolated from BALB/c mice were transfected with miR-155 mimic or inhibitor. Levels of suppressor of cytokine signaling 1/Janus kinase/signal transducer and activator of transcription (SOCS1/JAK/STAT) proteins and surface molecules (MHC-II, CD40, and CD86) were then measured. T-cell proliferation and apoptosis were evaluated in mixed lymphocyte reactions. Orthotopic liver transplantation was performed in mice after miR-155 short hairpin RNA lentivirus treatment, and postoperative survival, liver function and histology, and mRNA and protein expression were analyzed.
  
  
  RESULTS
  miR-155 knockdown in KCs decreased MHC-II, CD40, and CD86 expression, suppressed antigen-presenting function, and affected SOCS1/JAK/STAT inflammatory pathways. In addition, KCs transfected with miR-155 inhibitor and cocultured with T lymphocytes showed reduced T-cell responses but a greater number of apoptotic T cells. Finally, miR-155 suppression in graft liver prolonged liver allograft survival and improved liver function. The changes were closely associated with the levels of T helper 1 and 2 (Th1/Th2) cytokines and T-cell apoptosis, but a direct mechanistic link in vivo was not established.
  
  
  CONCLUSIONS
  These data suggest miR-155 regulates the balance of Th1/Th2 cytokines and the maturation and function of KCs in mice. miR-155 repression in KCs positively regulates KC function toward immunosuppression and prolongs liver allograft survival.
authors: Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Jinzheng
authors: J
authors: Li
authors: Junhua
authors: J
authors: Gong
authors: Peizhi
authors: P
authors: Li
authors: Min
authors: M
authors: Li
authors: Yiming
authors: Y
authors: Liu
authors: Shaoyong
authors: S
authors: Liang
authors: Jianping
authors: J
authors: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism*; D016031:Liver Transplantation / Q000009:adverse effects*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D035683:MicroRNAs / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D050791:STAT Transcription Factors; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases