The molecular mechanism of inhibition of interleukin-1beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract

Inflamm Res. 1999 Nov;48(11):575-81. doi: 10.1007/s000110050506.

Abstract

Objective: Several extracts of Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in patients with rheumatoid arthritis. We investigated the effect of multi-glycosides ofTWHF (GTW), a TWHF extract, on interleukin (IL)-1beta stimulated human rheumatoid synovial cells.

Materials and methods: IL-1beta-stimulated synovial cells were used to detect the effects of GTW on cyclooxygenase (COX)-1 and COX-2 activities, expression of COX protein and mRNA, and nuclear transcription factors in experiments using respective reporter plasmids.

Results: GTW inhibited prostaglandin E2 production by IL-1beta-stimulated synovial cells in a concentration-dependent manner, and also inhibited COX-2 protein and mRNA expression in a similar fashion to dexamethasone. However, GTW did not act as a glucocorticoid agonist. GTW repressed IL-1beta-induced nuclear factor-kappaB activity, but did not have a significant influence on activating protein-1 activity.

Conclusion: The anti-rheumatic effect of GTW or TWHF may be partly mediated through the inhibition of prostaglandin E2 production in human synovial cells due to suppression of COX-2 mRNA, possibly via inhibition of nuclear factor-kappaB activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Arthritis, Rheumatoid / metabolism
  • Blotting, Northern
  • Blotting, Western
  • COS Cells
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dexamethasone / pharmacology
  • Dinoprostone / biosynthesis
  • Gene Expression Regulation / drug effects
  • Genes, Reporter / genetics
  • Humans
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / pharmacology
  • Isoenzymes / biosynthesis*
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Membrane Proteins
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • RNA, Messenger / biosynthesis
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism*
  • Transcription Factors / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • Plant Extracts
  • RNA, Messenger
  • Transcription Factors
  • Dexamethasone
  • Luciferases
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone