Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model.

Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. Research Abstract Details 

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Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. Abstract Text:

Xiu-Da Shen,Bibo Ke,Yuan Zhai,Feng Gao,Sei-Ichiro Tsuchihashi,Charles R Lassman,Ronald W Busuttil,Jerzy W Kupiec-Weglinski,Xiu-Da Shen,Bibo Ke,Yuan Zhai,Feng Gao,Sei-Ichiro Tsuchihashi,Charles R Lassman,Ronald W Busuttil,Jerzy W Kupiec-Weglinski,

This study analyzes how toll-like receptor 4 (TLR4) signaling in the donor organ affects the ischemia and reperfusion injury (IRI) sequel following liver transplantation. Isogenic orthotopic liver transplantations (OLTs) with rearterialization were performed in groups of wild-type (WT) and TLR4 knockout (KO) mice after donor liver preservation in University of Wisconsin solution at 4 degrees C for 24 hours. Unlike WT OLTs, TLR4-deficient OLTs transplanted to either WT or TLR4 KO recipients suffered significantly less hepatocellular damage, as evidenced by serum alanine aminotransferase levels, and histological Suzuki's grading of liver IRI. Disruption of TLR4 signaling in OLTs decreased local neutrophil sequestration, CD4+ T cell infiltration, interferon (IFN)-gamma-inducible protein 10 (CXCL10) and an intercellular adhesion molecule (ICAM-1), as well as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, and IFN-gamma, yet increased IL-4 and IL-10 expression. The well-functioning OLTs from TLR4 KO donors revealed attenuated activity of capase-3, and enhanced heme oygenase-1 (HO-1) expression, along with decreased levels of apoptotic endothelial cells/hepatocytes, as compared with WT OLTs with intact TLR4 signaling. Thus, the functional sentinel TLR4 complex in the donor organ plays a key role in the mechanism of hepatic IRI after OLT. Disruption of TLR4 pathway downregulated the early proinflammatory responses and ameliorated hepatic IRI. These results provide the rationale to locally modify innate TLR4 signaling in the donor organ to more efficiently control the adaptive posttransplantation IRI-dependent responses.

Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. Publishing Authors By Initials

XD Shen,B Ke,Y Zhai,F Gao,S Tsuchihashi,CR Lassman,RW Busuttil,JW Kupiec-Weglinski,XD Shen,B Ke,Y Zhai,F Gao,S Tsuchihashi,CR Lassman,RW Busuttil,JW Kupiec-Weglinski,

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Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Liver transplantation : official publication of th

VOLUME: 13

Page Numbers: 1435-43

Journal Abbreviation: Liver Transpl.

ISSN: 1527-6465

DAY: 3

MONTH: Oct

YEAR: 2007

Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. Information

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LANGUAGE: eng

NlmUniqueID: 100909185

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Grant and Affiliation Information for Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model.

AFFILIATION: Dumont-University of California, Los Angeles (UCLA) Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.

Country: United States

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MEDLINETA: Liver Transpl

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