Toll-like receptors in liver ischemia reperfusion injury: a novel target for therapeutic modulation?

Expert Opin Ther Targets. 2009 Apr;13(4):427-42. doi: 10.1517/14728220902794939.

Abstract

Background: There is increasing evidence that Toll-like receptors (TLRs) sense host tissue damage by engaging with endogenous ligands. TLRs are considered to be involved in many primarily non-immune-related diseases. Hepatic ischemia reperfusion injury (IRI) represents one of these disorders.

Objective: To present the latest findings supporting the involvement of TLRs in liver IRI and to explore their role as potential targets for therapeutic intervention.

Methods: A review of the literature summarizing the latest advances in TLR signaling, the role of TLRs in each hepatic cell population and the involvement of TLRs in the pathophysiology of hepatic IRI. The potential role of TLR-targeting treatment strategies in liver IRI is discussed.

Conclusions: Recent experimental evidence suggests that TLR activation on Kupffer cells provides the triggering signal for pro-inflammatory responses that lead to liver IRI. Modulating TLR signaling could have a beneficial effect in patients with liver IRI.

Publication types

  • Review

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use
  • Adaptor Proteins, Vesicular Transport / physiology
  • Animals
  • Communicable Diseases / immunology
  • Dendritic Cells / physiology
  • Drosophila Proteins / physiology
  • Endothelial Cells / physiology
  • Epithelial Cells / physiology
  • Hepatic Stellate Cells / physiology
  • Hepatocytes / physiology
  • Humans
  • Inflammation / physiopathology
  • Kupffer Cells / physiology
  • Ligands
  • Liver / blood supply*
  • Liver / immunology
  • Liver Transplantation
  • Mammals / physiology
  • Mice
  • Myeloid Differentiation Factor 88 / physiology
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology
  • Toll-Like Receptors / classification
  • Toll-Like Receptors / drug effects*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / physiology

Substances

  • Adaptor Proteins, Vesicular Transport
  • Drosophila Proteins
  • Ligands
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptors
  • Acetylcysteine