title: Triptolide protects mice from ischemia/reperfusion injury by inhibition of IL-17 production.
abstract: Ischemia and reperfusion have been identified as a complex cascade of inflammatory mediators that are involved in the pathogenesis of hepatic injury. Triptolide (diterpenoid triepoxide), was extracted from a purified component of a traditional Chinese Medicine, Tripterygium wilfondii Hook F. Currently, triptolide has been shown to have anti-inflammatory, immunosuppressive, and antineoplastic activity. Accumulated data have shown that Th17 cells might contribute to the pathogenesis of liver diseases. Triptolide has been shown to reduce interleukin (IL)-17 expression in inflammatory bowel disease and arthritis. However, the role of triptolide in liver ischemia/reperfusion (I/R) and whether it can attenuate injury and the potential mechanism have not been investigated. Mice were treated with triptolide (0.1mg/kg) for 1 week or IL-17 antibody (50 μg/mouse) 2 days before ischemic insult. Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90 min, followed by various periods of reperfusion. We demonstrated that IL-17 was involved in the inflammatory response to hepatic I/R injury, and that triptolide inhibited IL-17 generation and suppressed neutrophil migration after liver I/R injury through downregulation of signal transducer and activator of transcription 3 (STAT3) transcription. Also, triptolide pretreatment protected the liver from warm I/R injury, at least in part, mediated by the upregulation of Foxp3 expression. These results could pave the way for the use of triptolide as a novel agent to attenuate I/R injury.
authors.affiliation: Department of Liver Transplantation, the First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China.
authors.forename: Chuanxing
authors.initials: C
authors.lastname: Wu
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Xia
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000302:isolation & purification; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000302:isolation & purification; D008517:Phytotherapy; D015427:Reperfusion Injury / Q000517:prevention & control; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D029757:Tripterygium / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004224:Diterpenes; D004852:Epoxy Compounds; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D010616:Phenanthrenes; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C001899:triptolide