Diverse effects of FK506 on the apoptosis of hepatocytes and infiltrating lymphocytes in an allografted rat liver.
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.
Moriuchi
Hiroki
H
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Saga, Japan. mkaki1@mac.com
Kamohara
Yukio
Y
Eguchi
Susumu
S
Gu
Weili
W
Fujioka
Hikaru
H
Yamamoto
Takao
T
Tajima
Yoshitsugu
Y
Kanematsu
Takashi
T
Koji
Takehiko
T
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
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