title: Diverse effects of FK506 on the apoptosis of hepatocytes and infiltrating lymphocytes in an allografted rat liver.
abstract: BACKGROUND
  The current study investigated whether FK506 (FK) regulates the apoptotic systems in allografted rat liver and the contribution of Fas/Fas-ligand system and Bcl-2 family during acute rejection.
  
  
  METHODS
  The recipients were divided into three groups, the allo, the allo-FK, and the syn group. Rats were euthanized 1, 3, 5, and 7 d after OLT. Apoptotic activity was explored using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The expression of Fas/Fas-ligand and Bcl-2/Bax in the grafted livers was investigated by Western blotting and immunohistochemistry.
  
  
  RESULTS
  The apoptotic index (AI) of hepatocytes in the allo-FK group was less than that in the allo group. Fas in the allo group was more intense than that in the allo-FK group in the periportal areas on day 1 and 3, while Bcl-2 in the allo group was less intense than that in the allo-FK group in the pericaval areas at all time-points after OLT.
  
  
  CONCLUSIONS
  FK provides beneficial antiapoptotic effects on hepatocytes in the grafted rat livers through both the down-regulation of Fas expression in the periportal areas and the up-regulation of Bcl-2 expression in the pericaval areas.
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Saga, Japan. mkaki1@mac.com
authors.forename: Hiroki
authors.initials: H
authors.lastname: Moriuchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kamohara
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
authors.forename: Weili
authors.initials: W
authors.lastname: Gu
authors.forename: Hikaru
authors.initials: H
authors.lastname: Fujioka
authors.forename: Takao
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Tajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D053222:Fas Ligand Protein / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016031:Liver Transplantation / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D016559:Tacrolimus