HO-1 upregulation suppresses type 1 IFN pathway in hepatic ischemia/reperfusion injury

S. Tsuchihashi, Y. Zhai, C. Fondevila, R. W. Busuttil, J. W. Kupiec-Weglinski

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Upregulation of heme oxygenase (HO)-1, a heat shock protein 32, protects against hepatic ischemia/reperfusion (I/R) injury. Activation of "innate" toll-like receptor (TLR) 4 system triggers the I/R injury cascade. This study explores cytoprotective functions of HO-1 overexpression following exogenous administration of cobalt protoporphyrin (CoPP), and its relationship with the TLR4 pathway in a model of mouse partial hepatic warm I/R injury. CoPP treatment markedly improved hepatic function and histology, and suppressed pro-inflammatory cytokine elaboration profile, as compared with untreated controls. Although administration of CoPP did not affect intrahepatic TLR4, it downregulated IFN-inducible protein 10 (IP-10) expression. As IP-10 is the major product of type-1 IFN pathway downstream of TLR4, we then infused recombinant IFN-β (rIFN-β) directly into mouse livers. Interestingly, infusion of rIFN-β upregulated hepatic IP-10 expression. In contrast, adjunctive CoPP treatment decreased IP-10 levels in mouse livers infused with rIFN-β. Thus, CoPP-induced HO-1 upregulation suppresses type-1 IFN pathway downstream of TLR4 system in hepatic warm I/R injury model.

Original languageEnglish (US)
Pages (from-to)1677-1678
Number of pages2
JournalTransplantation Proceedings
Volume37
Issue number4
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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