Activation of innate immunity (NK/IFN-γ) in rat allogeneic liver transplantation: Contribution to liver injury and suppression of hepatocyte proliferation

Kezhen Shen, Shu Sen Zheng, Ogyi Park, Hua Wang, Zhaoli Sun, Bin Gao

Research output: Contribution to journalArticle

Abstract

Liver transplantation is presently the only curative treatment for patients with end-stage liver disease. However, the mechanisms underlying liver injury and hepatocyte proliferation posttransplantation remain obscure. In this investigation, liver injury and hepatocyte proliferation in syngeneic and allogeneic animal models were compared. Male Lewis and Dark Agouti (DA) rats were subjected to orthotopic liver transplantation (OLT). Rat OLT was performed in syngeneic (Lewis-Lewis) and allogeneic (Lewis-DA or DA-Lewis) animal models. Allogeneic liver grafts exhibited greater injury and cellular apoptosis than syngeneic grafts but less hepatocyte proliferation after OLT. Expression of IFN-γ mRNA and activation of the downstream signal transducer and activator of transcription 1 (STAT1) and genes (interferon regulatory factor-1 and cyclin-dependent kinase inhibitor p21CDKN1A) were also greater in the allogeneic grafts compared with the syngeneic grafts. In contrast, STAT3 activation was lower in the allogeneic grafts. Furthermore, in the allogeneic grafts, depletion of natural killer (NK) cells decreased IFN-γ/STAT1 activation but enhanced hepatocyte proliferation. These findings suggest that, compared with syngeneic transplantation, innate immunity (NK/IFN-γ) is activated after allogeneic transplantation, which likely contributes to liver injury and inhibits hepatocyte proliferation.

Original languageEnglish (US)
Pages (from-to)G1070-G1077
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • IRF-1
  • Liver regeneration
  • NK cells
  • STAT1
  • p21

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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