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Title

How ischaemic preconditioning protects small liver grafts

AuthorsFranco-Gou, Rosa ; Roselló-Catafau, Joan ; Casillas-Ramírez, Araní ; Massip-Salcedo, Marta ; Rimola, Antoni; Calvo, Naiara; Bartrons, Ramón; Peralta, Carmen
KeywordsIschaemia-reperfusion
IL-1
Liver regeneration
Oxidative stress
Reduced-size liver transplantation
HSP
Issue Date1-Nov-2005
PublisherJohn Wiley & Sons
CitationJournal of Pathology 208(1): 62-73 (2006)
AbstractInterleukin-1 (IL-1) and transforming growth factor-β (TGFβ) are key inhibitors of hepatocyte proliferation after hepatectomy. IL-1 inhibition by heat shock proteins (HSPs) has been reported in inflammatory processes. A recent study indicated the benefits of ischaemic preconditioning in reduced-size orthotopic liver transplantation (ROLT). The present study examined: (a) the effect of ischaemic preconditioning on IL-1 and TGFβ in ROLT; (b) whether preconditioning protects small liver grafts through HSP induction; and (c) whether the potential benefits of preconditioning on HSP is related to IL-1 inhibition. Our results, obtained with an IL-1 receptor antagonist, indicated the injurious effects of IL-1 in ischaemia-reperfusion (I/R) injury and established a relationship between IL-1 and growth factors. Thus, IL-1 reduced hepatocyte growth factor (HGF) and promoted TGFβ release, thus contributing to the impaired liver regeneration associated with ROLT. Preconditioning inhibited IL-1 through nitric oxide (NO), thereby protecting against the injurious effects of IL-1. In addition, by another pathway independent of NO, preconditioning induced HSP70 and haem-oxygenase-1 (HO-1). HO-1 protected against I/R injury and liver regeneration, whereas the benefits resulting from HSP70 were mainly related to hepatocyte proliferation. These results suggest a mechanism that explains the effectiveness of preconditioning in ROLT. They suggest, too, that other strategies, in addition to preconditioning, that modulate IL-1 and/or HSPs could be considered in clinical situations requiring liver regeneration such as small liver grafts. Copyright © 2005 Pathological Society of Great Britain and Ireland.
Publisher version (URL)http://dx.doi.org/10.1002/path.1859
URIhttp://hdl.handle.net/10261/114045
DOIhttp://dx.doi.org/10.1002/path.1859
Identifiersdoi: 10.1002/path.1859
issn: 0022-3417
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