Triptolide protects mice from ischemia/reperfusion injury by inhibition of IL-17 production.

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.