[Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts].
OBJECTIVE
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).


CONCLUSIONS
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.
Mao
Xiao-dan
XD
The Obstetrics and Gynecology Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China. aimaoxiaodan@hotmail.com
Sun
Sai-jun
SJ
Pei
Zi-yan
ZY
Zhang
Li-huang
LH
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020382:Interleukin-18 / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010616:Phenanthrenes / Q000494:pharmacology*; D053724:Receptors, Interleukin-18 / Q000037:antagonists & inhibitors*; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology
D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D016328:NF-kappa B; D010616:Phenanthrenes; D053724:Receptors, Interleukin-18; C001899:triptolide