Protective effect of lipopolysaccharide preconditioning in hepatic ischaemia reperfusion injury
Preconditioning using lipopolysaccharide (LPS), a toll-like receptor4 (TLR4) ligand, has been demonstrated to reduce ischaemia/reperfusion injury (IRI) in some organs, but its effect in the liver has not been elucidated. We examined the liver protective mechanism and correlated signalling pathway of...
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Published in | HPB (Oxford, England) Vol. 12; no. 8; pp. 538 - 545 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Elsevier Ltd
01.10.2010
Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Preconditioning using lipopolysaccharide (LPS), a toll-like receptor4 (TLR4) ligand, has been demonstrated to reduce ischaemia/reperfusion injury (IRI) in some organs, but its effect in the liver has not been elucidated. We examined the liver protective mechanism and correlated signalling pathway of LPS preconditioning in mice.
BALB/c and TLR4 mutant mice underwent 90min of 70% hepatic ischaemia. Lipopolysaccharide (100µg/kg) was injected intraperitoneally 20h or 30min before ischaemia. Liver damage after reperfusion was examined using serum samples and liver specimens. To analyse the mechanism of preconditioning in detail, phosphorylation of representative signalling mediators to nuclear factor-κB (NF-κB) activation, Akt and interleukin-1 receptor-associated kinase-1 (IRAK-1), and expression of a negative feedback inhibitor, suppressor of cytokine signalling-1 (SOCS-1), were evaluated by Western blotting.
Pretreatment with LPS only 20h before ischaemia elicited a preconditioning effect; however, preconditioning was absent in TLR4 mutant mice. Lipopolysaccharide significantly decreased serum alanine aminotransferase, tumour necrosis factor-α, hepatocyte necrosis and NF-κB activity after reperfusion. Phosphorylated IRAK-1 was suppressed by LPS, whereas no difference was observed in phosphorylated Akt. Pre-ischaemic LPS provided early induction of SOCS-1.
Late-phase LPS preconditioning provided liver protection against IRI through the downregulation of the TLR4 cascade derived from early induction of SOCS-1 during ischaemia/reperfusion. |
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Bibliography: | istex:7C04BB874218A44C65C6D6A80C94D636CA6B589D ark:/67375/WNG-FP87K4XT-Q ArticleID:HPB211 This paper was presented at the International Hepato‐Pancreato‐Biliary Association Meeting, 18–22 April 2010, Buenos Aires, Argentina. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This paper was presented at the International Hepato-Pancreato-Biliary Association Meeting, 18–22 April 2010, Buenos Aires, Argentina. |
ISSN: | 1365-182X 1477-2574 |
DOI: | 10.1111/j.1477-2574.2010.00211.x |