FK506 promotes liver regeneration by suppressing natural killer cell activity.
We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-beta 1 (TGF-beta 1) and found no changes in HGF and TGF-beta 1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.
First Department of Internal Medicine, Yamaguchi University, School of Medicine, Japan.
F
F
Tamura
A
A
Masuhara
I
I
Sakaida
E
E
Fukumoto
T
T
Nakamura
K
K
Okita
D000818:Animals; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D016559:Tacrolimus