title: Linking proximal and downstream signalling events in hepatic ischaemia/reperfusion injury.
abstract: Hepatic I/R (ischaemia/reperfusion) injury occurs in a variety of clinical settings including transplantation, elective liver resections and trauma. One of the challenges in studying the pathophysiology of I/R injury is the fact that the liver plays a central role in a variety of metabolic pathways in addition to governing aspects of immune surveillance and tolerance. The pathways activated in response to insults as varied as toxins, microbial and endogenous ligands and I/R may share common elements. The multiple intracellular signalling cascades involved in this process and the initiating events are still under investigation. Recent work on the role of TLRs (Toll-like receptors) in I/R injury has elucidated some of the more proximal signalling events in the pathway. In addition to the well-established role of signalling molecules such as NO (nitric oxide) in mediating damage or protection following hepatic I/R, more recent studies have focused on the participation of endogenous danger signals or DAMPs (damage-associated molecular patterns) such as HMGB1 (high-mobility group box 1). The complex interplay between HMGB1, TLRs and the many intracellular signalling molecules and pathways is illustrative of how our understanding of hepatic I/R injury is continually evolving.
authors.affiliation: Department of Surgery, University of Pittsburgh, School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA.
authors.forename: G
authors.initials: G
authors.lastname: Jeyabalan
authors.forename: A
authors.initials: A
authors.lastname: Tsung
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II