Interleukin-6 and STAT3 protect the liver from hepatic ischemia and reperfusion injury during ischemic preconditioning

Tadashi Matsumoto; Kerri O'Malley; Philip A Efron; Colette Burger; Priscilla F McAuliffe; Philip O Scumpia; Takefumi Uchida; Sven K Tschoeke; Shiro Fujita; Lyle L Moldawer; Alan W Hemming; David P Foley

doi:10.1016/j.surg.2006.04.010

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Interleukin-6 and STAT3 protect the liver from hepatic ischemia and reperfusion injury during ischemic preconditioning

Journal article

Peer reviewed

Interleukin-6 and STAT3 protect the liver from hepatic ischemia and reperfusion injury during ischemic preconditioning

Tadashi Matsumoto, Kerri O'Malley, Philip A Efron, Colette Burger, Priscilla F McAuliffe, Philip O Scumpia, Takefumi Uchida, Sven K Tschoeke, Shiro Fujita, Lyle L Moldawer, …

Surgery, Vol.140(5), pp.793-802

11/2006

DOI: 10.1016/j.surg.2006.04.010

PMID: 17084723

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Abstract

Ischemic preconditioning has been shown to protect the liver from ischemia/reperfusion injury. We hypothesized that IL-6 directly modulates the protective effects of ischemic preconditioning. Three weeks after undergoing splenic transposition, wild-type C57BL/6 and IL-6 null mice underwent 75 minutes of total hepatic ischemia with or without prior ischemic preconditioning (10 minutes of ischemia followed by 15 minutes of reperfusion). After reperfusion, serum ALT, serum IL-6, hepatic IL-6 mRNA, hepatic pSTAT3, and liver histology were evaluated. In wild-type mice, survival at 24 hours was greater in the preconditioned group compared with the non-preconditioned group (75% vs 40%, P<.05). In IL-6 null mice, however, ischemic preconditioning did not improve survival when compared with the non-preconditioned group. Preconditioning significantly reduced hepatocellular injury in wild-type mice (P<.05) when compared with IL-6 null animals. This protection was associated with significant increases in serum IL-6, hepatic IL-6 mRNA, and hepatic pSTAT3 levels (P<.05). The protective effects of ischemic preconditioning that correlated with significant increases in systemic IL-6, hepatic IL-6 mRNA abundance, and pSTAT3 levels, were not observed in IL-6 null mice. The protective effects of ischemic preconditioning during total hepatic ischemia/reperfusion injury are dependent on IL-6 signaling and are associated with increased phosphorylation of hepatic STAT3.

Alanine Transaminase - blood

Animals

Female

Interleukin-6 - blood

Interleukin-6 - metabolism

Interleukin-6 - physiology

Ischemia - pathology

Ischemia - prevention & control

Ischemic Preconditioning

Liver - blood supply

Liver - metabolism

Liver - pathology

Mice

Mice, Inbred C57BL

Mice, Knockout

Reperfusion Injury - pathology

Reperfusion Injury - prevention & control

RNA, Messenger - metabolism

STAT3 Transcription Factor - physiology

Details

Title: Subtitle: Interleukin-6 and STAT3 protect the liver from hepatic ischemia and reperfusion injury during ischemic preconditioning
Creators: Tadashi Matsumoto - University of Florida
Kerri O'Malley
Philip A Efron - University of Florida
Colette Burger - University of Florida
Priscilla F McAuliffe - University of Florida
Philip O Scumpia - University of Florida
Takefumi Uchida - University of Florida
Sven K Tschoeke - University of Florida
Shiro Fujita - University of Florida
Lyle L Moldawer - University of Florida
Alan W Hemming - University of Florida
David P Foley - University of Florida
Resource Type: Journal article
Publication Details: Surgery, Vol.140(5), pp.793-802
DOI: 10.1016/j.surg.2006.04.010
PMID: 17084723
ISSN: 0039-6060
eISSN: 1532-7361
Grant note: R01 GM-63041-06 / NIGMS NIH HHS R37 GM-40561-18 / NIGMS NIH HHS T32-GM-08721 / NIGMS NIH HHS
Language: English
Date published: 11/2006
Academic Unit: Surgery
Record Identifier: 9984322937002771

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