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Inflammation Research

, Volume 57, Issue 6, pp 260–265 | Cite as

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

  • Y. Lu
  • W.-J. Wang
  • J.-H. Leng
  • L.-F. Cheng
  • L. Feng
  • H.-P. Yao
Article

Abstract.

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).

Materials and Methods:

RASF were obtained from the synovial tissue of patients with RA. RASF were pretreated with TP (0~100 ng/ml) for 2 h before stimulation with PMA (50 ng/ml). The bioactivity of IL-18 in the supernatant was detected based on IFN-γ secretion from IL-18-responding human myelomonocytic KG-1 cells. IL-18 level was analyzed by ELISA. In situ expression of IL-18Rα was determined by immunofluorescence assay. To estimate the protein and mRNA expression of IL-18 and IL-18Rα in RASF, western blot and quantitative RT-PCR were performed. Nuclear factor-κB (NF-κB) 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-κB activity in PMA-stimulated RASF was profoundly suppressed by TP. These effects showed a high correlation with TP concentration (0~100 ng/ml).

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.

Keywords:

Triptolide Rheumatoid arthritis Synovial fibroblasts Interleukin-18 Interleukin-18 receptor 

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Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • Y. Lu
    • 1
  • W.-J. Wang
    • 2
  • J.-H. Leng
    • 3
  • L.-F. Cheng
    • 1
  • L. Feng
    • 1
  • H.-P. Yao
    • 1
  1. 1.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Center of Clinic Experiment Medicine, the First Affiliated HospitalZhejiang University School of MedicineZhejiangChina
  3. 3.Center of Clinic Experiment Medicine, Hangzhou First People HospitalHangzhouChina

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