Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury.

Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Research Abstract Details 

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Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Abstract Text:

Allan Tsung,Ning Zheng,Geetha Jeyabalan,Kunihiko Izuishi,John R Klune,David A Geller,Michael T Lotze,Lina Lu,Timothy R Billiar,

Endogenous ligands released from damaged cells, so-called damage-associated molecular pattern molecules (DAMPs), activate innate signaling pathways including the TLRs. We have shown that hepatic, warm ischemia and reperfusion (I/R) injury, generating local, noninfectious DAMPs, promotes inflammation, which is largely TLR4-dependent. Here, we demonstrate that increasing dendritic cell (DC) numbers enhance inflammation and organ injury after hepatic I/R. High-mobility group box 1 (HMGB1), a NF released by necrotic cells or secreted by stimulated cells, is one of a number of ligands promoting TLR4 reactivity. Augmentation of DC numbers in the liver with GM-CSF hydrodynamic transfection significantly increased liver damage after I/R when compared with controls. TLR4 engagement on hepatic DC was required for the I/R-induced injury, as augmentation of DC numbers in TLR4 mutant (C3H/HeJ) mice did not worsen hepatic damage. It is interesting that TLR4 expression was increased in hepatic DC following HMGB1 stimulation in vitro, suggesting a mechanism for the increased liver injury following I/R. It thus appears that functional TLR4 on DC is required for I/R-induced injury. Furthermore, HMGB1 may direct the inflammatory responses mediated by DC, at least in part, by enhancing TLR4 expression and reactivity to it and other DAMPs.

Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Publishing Authors By Initials

A Tsung,N Zheng,G Jeyabalan,K Izuishi,JR Klune,DA Geller,MT Lotze,L Lu,TR Billiar,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of leukocyte biology

VOLUME: 81

Page Numbers: 119-28

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 24

MONTH: 10

YEAR: 2006

Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8405628

Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: physiology

Chemical & Substance for Abstract: Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury. Information

Substance Name: Granulocyte-Macrophage Colony-Stimulatin

Registry Number: 83869-56-1

Grant and Affiliation Information for Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury.

AFFILIATION: Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R01-GM52021

ACRONYM: GM

MEDLINETA: J Leukoc Biol

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