Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Jul;25(7):606-8, 611
Authors: Mao XD, Sun SJ, Pei ZY, Zhang LH

AIM: To determine the effects of triptolide (TP) on the expression of interleukin-18 (IL-18) and its receptor in phorbol 12-myristate 13-acetate (PMA)-stimulated rheumatoid arthritis synovial fibroblasts (RASF). METHODS: RASF were pretreated with TP (0-100 microg/L) for 2 h before stimulation with PMA (50 microg/L). The bioactivity of IL-18 in the supernatant was detected based on IFN-gamma secretion from IL-18-responding human myelomonocytic KG-1 cells. IL-18 level was analyzed by ELISA. To estimate the protein and mRNA expression of IL-18 and IL-18Ralpha in RASF, Western blot and quantitative RT-PCR were performed. Nuclear factor-kappaB (NF-kappaB) activity in the whole-cell extract of treated RASF was also measured using an ELISA-based method. RESULTS: TP effectively inhibited the bioactivity of IL-18 in PMA-stimulated RASF. The expression of IL-18 and IL-18R at protein and gene levels was reduced by TP. NF-kappaB activity in PMA-stimulated RASF was profoundly suppressed by TP. These effects showed a high correlation with TP concentration (0-100 microg/L). CONCLUSION: TP effectively inhibited the expression of IL-18 and its receptor in PMA-stimulated RASF. These results suggest a mechanism of TP in RA therapy.

PMID: 19737478 [PubMed – indexed for MEDLINE]