Faculty Collaboration Database

STAT3 does not regulate acute liver injury after ischemia/reperfusion. J Surg Res 2011 Dec;171(2):814-8

Date

07/06/2010

Pubmed ID

20599212

Pubmed Central ID

PMC2965827

DOI

10.1016/j.jss.2010.04.006

Scopus ID

2-s2.0-81155153772 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a serious complication of liver surgery and transplantation. Regulation of this injury response occurs at the cellular and molecular levels. Previous studies have shown that interleukin-6 (IL-6) is a negative regulator of the acute inflammatory injury occurring as a result of hepatic I/R. The signal transducer and activator of transcription-3 (STAT3) is a key target of receptor signaling for IL-6. Both IL-6 and STAT3 have been implicated in the protective effects of ischemic preconditioning of the liver. However, there have been no studies that have directly addressed the potential role of STAT3 in regulating acute inflammatory liver injury induced by I/R. In the current study, we investigated whether blockade of STAT3 phosphorylation altered the injury response to hepatic I/R injury.

METHODS: Male Balb/c mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion with or without treatment with specific inhibitors of STAT3 activation, AG490 (selective JAK2 inhibitor), or STATTIC (direct inhibitor of STAT3 phosphorylation). Mice were sacrificed at 8 and 24 h after reperfusion.

RESULTS: STAT3 activation was induced by I/R. This activation was partially inhibited by administration of AG490 and almost completely abrogated by treatment with STATTIC. Despite the blockade of STAT3, neither AG490 nor STATTIC had any effect on acute liver injury induced by I/R. Treatment with STATTIC did reduce hepatic neutrophil accumulation.

CONCLUSION: The data suggest that STAT3 is not a central regulator of acute liver injury induced by I/R.

Author List

Clarke C, Sakai N, Tevar AD, Schuster R, Edwards MJ, Lentsch AB

Author

Callisia N. Clarke MD Chief, Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Cyclic S-Oxides
Enzyme Inhibitors
Hepatitis
Janus Kinase 2
Male
Mice
Mice, Inbred BALB C
Neutrophils
Phosphorylation
Reperfusion Injury
STAT3 Transcription Factor
Tyrphostins