title: Effects of trichostatin A in a rat model of acute graft-versus-host disease after liver transplantation.
abstract: BACKGROUND
  Acute graft-versus-host disease (aGVHD) is a rare but serious and life-threatening complication of liver transplantation (LTx). Previously, we have demonstrated that the development of aGVHD after LTx (LTx-aGVHD) is associated with a decreased percentage of regulatory T cells (Tregs) in the peripheral blood of recipients. Histone deacetylase inhibitors promote the production of Tregs and some, such as suberoylanilide hydroxamic acid and trichostatin A (TSA), are used to treat autoimmune diseases, including GVHD after bone marrow transplantation.
  
  
  METHODS
  In this study, LTx-aGVHD rats were treated with TSA continuously for 7 days from day 8 to 14 after LTx. Subsequently, splenic T cells were used for in vitro investigations of the mechanism of action of transplantation.
  
  
  RESULTS
  All LTx-aGVHD rats developed typical LTx-aGVHD symptoms after TSA treatment and died from LTx-aGVHD. The percentage frequency of Tregs in peripheral blood mononuclear cells was slightly up-regulated after TSA treatment, whereas TSA dramatically down-regulated Foxp3 protein and mRNA levels both in vivo and in vitro. Furthermore, TSA impaired T-cell proliferation and production of proinflammatory and anti-inflammatory cytokines in vitro.
  
  
  CONCLUSIONS
  TSA does not abrogate LTx-aGVHD in rats due to down-regulation of Tregs.
authors.affiliation: Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.forename: Qida
authors.initials: Q
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xueli
authors.initials: X
authors.lastname: Bai
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
mesh_terms: D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D017211:Treatment Failure
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A