Up regulation of IL-6 by ischemic preconditioning in normal and fatty rat livers: association with reduction of oxidative stress.
We analyzed the role of IL-6 in the protection that ischemic preconditioning (IP) exerts against hepatic ischemia reperfusion-mediated (I/R) oxidative damage, particularly in fatty livers. IP-related IL-6 up-regulation during reperfusion in steatotic and non-steatotic livers was correlated with reduced indices of liver damage, as also demonstrated by pharmacological modulation of IL-6. IP activated NF-kB and HSF during ischemia (Isc), whereas AP-1 activity was unaffected. IP blunted the activation of STAT3 and stress-responsive genes, such as NF-kB, AP-1 and heme oxygenase (HO-1) during reperfusion. The role of reduced oxidative stress in hepatoprotection of fatty livers was further demonstrated by the fact that: (i) IP prevented the decrease of glutathione levels and the increase of lipid peroxidation; (ii) the anti-oxidant GSH-ester prevented lipid peroxidation and necrosis. In conclusion, IP modulates the activity of transcription factors and triggers IL-6 production; this may prevent hepatic I/R damage in a oxidative stress-dependent way, particularly in fatty livers.
Tacchini
Lorenza
L
Institute of General Pathology, University of Milano, via Mangiagalli 31, 20133, Milano, Italy.
Cairo
Gaetano
G
De Ponti
Cristina
C
Massip
Marta
M
Rosellò-Catafau
Joan
J
Peralta
Carmen
C
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology; D014158:Transcription, Genetic; D015854:Up-Regulation
D015850:Interleukin-6; D051547:Heme Oxygenase-1; D005978:Glutathione