title: STAT3 does not regulate acute liver injury after ischemia/reperfusion.
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.
  
  
  CONCLUSIONS
  The data suggest that STAT3 is not a central regulator of acute liver injury induced by I/R.
authors.affiliation: The Laboratory of Trauma, Sepsis & Inflammation Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA.
authors.forename: Callisia
authors.initials: C
authors.lastname: Clarke
authors.forename: Nozomu
authors.initials: N
authors.lastname: Sakai
authors.forename: Amit D
authors.initials: AD
authors.lastname: Tevar
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schuster
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000208:Acute Disease; D000818:Animals; D003499:Cyclic S-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D003499:Cyclic S-Oxides; D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C517409:stattic; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2