title: Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver.
abstract: Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury.
authors.affiliation: Department of Biomedical Sciences and Biotechnology, Division of General Pathology and Immunology, University of Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tiberio
authors.forename: Guido A M
authors.initials: GA
authors.lastname: Tiberio
authors.forename: Lidia
authors.initials: L
authors.lastname: Bardella
authors.forename: Edoardo
authors.initials: E
authors.lastname: Cervi
authors.forename: Katia
authors.initials: K
authors.lastname: Cerea
authors.forename: Michel
authors.initials: M
authors.lastname: Dreano
authors.forename: Gianni
authors.initials: G
authors.lastname: Garotta
authors.forename: Anna
authors.initials: A
authors.lastname: Fra
authors.forename: Nadia
authors.initials: N
authors.lastname: Montani
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari-Bravo
authors.forename: Francesco
authors.initials: F
authors.lastname: Callea
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Giulini
authors.forename: Luisa
authors.initials: L
authors.lastname: Schiaffonati
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011489:Protein Denaturation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D004247:DNA