Calcitriol prolongs recipient survival by inducing expression of zinc-finger protein A20 and inhibiting its downstream gene following rat orthotopic liver transplantation.
Calcitriol has important immunomodulation action and can prolong recipient survival after organ transplantation. The data in this study demonstrated that treatment of liver allograft recipient with calcitriol can protect allograft from acute rejection and prolong recipient's survival. Calcitriol inhibited expression of proinflammatory cytokine such as Interleukin-2 and Interferon-gamma intragraft. It also inhibited expression of nuclear factor kappaB (NF-kappaB) significantly as a result of enhancing its inhibitory protein I kappa B (IkappaB). As well, expression of zinc-finger protein A20 (A20) was enhanced significantly. The results suggest that calcitriol exerts its immunosuppression action in part through inducement of the A20, IkB, inhibition of NF-kB, and resultant proinflammatory expression pathway.
Zhang
Aibin
A
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhang
Mangli
M
Wang
Yan
Y
Xie
Haiyang
H
Zheng
Shusen
S
D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control*; D020672:I-kappa B Proteins / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D002120:Calcium Channel Agonists; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D007371:Interferon-gamma; C000602677:TNFAIP3 protein, rat; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D002117:Calcitriol