Background/Purpose: Th17 plays important role in pathogenesis of AS inflammation, and its main effector, IL-17, was the critical effector on mediating it. Activated of Th17 and IL-17 are both depending on JAK/STAT signal pathway. A cluster of recent papers identify Thunder God Vine as a powerful drug in AS treatment in China, in which Triptolide was demonstrated as the key ingredient in anti-inflammatory. This research aims to explore the role of Triptolide played in Th17 differentiation and AS inflammation by interfering the JAK/STAT.

Methods: 30 AS patients (18-50years) in active stage and 15 healthy controls (18-50years) participated in the experiments. All patients were met with the modified New York criteria(Bath Disease Activity Score>4). PBMCs generated from patients were cultivate with different concentrations of Triptolide for 24 hours (High: 50ng/ml; Medium: 25ng/ml; Low: 12.5ng/ml). The supernate level of IL-17 was detected by ELISA, the protein levels of JAK2/STAT3 signal pathway were detected by Western blotting, and the mRNA level of RORc was detected by quantitative PCR (qPCR).

Results: Compared with controls, the protein expression level of pJak2,pSata3,RORc was higher in AS groups than in normal ones(**p<0.001£©. After the intervention of the triptolide, protein expression level of pJak2,pSata3,RORc was lower than in AS groups.(#p<0.05). ( Figure1)

The transcriptional level of RORc mRNA was higher in AS groups than normal (**p<0.001£©.After the intervention of the triptolide, the transcriptional level of RORc mRNA was lower than in AS groups.(#p<0.05) ( Figure2).     The level of  IL-17 in active AS patients was higher than normal; (**p<0.001);after the intervention of the triptolide,the levels of IL-17 was lower than AS groups . (#p<0.05) ( Figure3).

Conclusion: Our findings showed the suppression of activated JAK2/STAT3 signal pathway and the depression of pJAK2 and pSTAT3 expression by Triptolide. It might be one of the inhibitive factor modulate RORc transcription on one hand, and could be an depressor in IL-17 secretion directly on another. Which suggesting Triptolide may probably regulates Th17 differentiation through JAK2/STAT3 signal pathway. That¡¯s one of molecular mechanism which it plays in relieving AS inflammation. These exciting findings have broad implications for the inhibitor of JAK/STAT signal pathway in AS targeted therapy.