Narci Teoh1, Jacqueline Field, Geoffrey Farrell. 1. Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.
Abstract
BACKGROUND/AIMS: The biological effects of ischaemic preconditioning include NF-kappaB activation, increased TNF synthesis, stimulation of cell cycle entry and hepatoprotection against ischaemia-reperfusion (IR) injury. Low dose TNF initiates the priming phase of liver regeneration via NF-kappaB and IL-6. To determine whether (1) IL-6 is released during preconditioning and confers protection against hepatic IR injury, and (2) IL-6 could mediate the biological effects of preconditioning. METHODS: Wildtype (wt) and TNF-/- C57BL6 mice were subjected to 90 min partial hepatic ischaemia and 2-44 h reperfusion with or without prior 10 min ischaemic preconditioning. To restitute liver injury, TNF-/- mice were administered murine TNF 5 microg/kg iv 1 min prior to IR. Murine recombinant IL-6 (500 ng/kg iv) was administered 30 min prior to IR, either to wt mice or to TNF-/--repleted mice; in the latter case, 1 min before preconditioning. RESULTS: In wt mice, IL-6 attenuated hepatic IR injury and stimulated cell cycle entry. IR injury in TNF-repleted TNF-/- mice was not ameliorated by preconditioning. However, prior IL-6 administration conferred hepatoprotection (IL-6/preconditioned: 349+/-169 U/L vs vehicle/preconditioned: 1250+/-608 U/L, P<0.01). CONCLUSIONS: IL-6 is one likely mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning.
BACKGROUND/AIMS: The biological effects of ischaemic preconditioning include NF-kappaB activation, increased TNF synthesis, stimulation of cell cycle entry and hepatoprotection against ischaemia-reperfusion (IR) injury. Low dose TNF initiates the priming phase of liver regeneration via NF-kappaB and IL-6. To determine whether (1) IL-6 is released during preconditioning and confers protection against hepatic IR injury, and (2) IL-6 could mediate the biological effects of preconditioning. METHODS: Wildtype (wt) and TNF-/- C57BL6 mice were subjected to 90 min partial hepatic ischaemia and 2-44 h reperfusion with or without prior 10 min ischaemic preconditioning. To restitute liver injury, TNF-/- mice were administered murineTNF 5 microg/kg iv 1 min prior to IR. Murine recombinant IL-6 (500 ng/kg iv) was administered 30 min prior to IR, either to wt mice or to TNF-/--repleted mice; in the latter case, 1 min before preconditioning. RESULTS: In wt mice, IL-6 attenuated hepatic IR injury and stimulated cell cycle entry. IR injury in TNF-repleted TNF-/- mice was not ameliorated by preconditioning. However, prior IL-6 administration conferred hepatoprotection (IL-6/preconditioned: 349+/-169 U/L vs vehicle/preconditioned: 1250+/-608 U/L, P<0.01). CONCLUSIONS:IL-6 is one likely mediator of the hepatoprotective and pro-proliferative effects of ischaemic preconditioning.
Authors: Benjamin H Friedman; Joshua H Wolf; Liqing Wang; Mary E Putt; Abraham Shaked; Jason D Christie; Wayne W Hancock; Kim M Olthoff Journal: Liver Transpl Date: 2012-02 Impact factor: 5.799
Authors: Vincent Braunersreuther; Giorgio Luciano Viviani; François Mach; Fabrizio Montecucco Journal: World J Gastroenterol Date: 2012-02-28 Impact factor: 5.742
Authors: Rebecca A Sosa; Ali Zarrinpar; Maura Rossetti; Charles R Lassman; Bita V Naini; Nakul Datta; Ping Rao; Nicholas Harre; Ying Zheng; Roberto Spreafico; Alexander Hoffmann; Ronald W Busuttil; David W Gjertson; Yuan Zhai; Jerzy W Kupiec-Weglinski; Elaine F Reed Journal: JCI Insight Date: 2016-12-08