title: The molecular mechanism of inhibition of interleukin-1beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medical Science, St Marianna University School of Medicine, Miyamae, Kawasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maekawa
authors.forename: N
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: S
authors.initials: S
authors.lastname: Nishida
authors.forename: H
authors.initials: H
authors.lastname: Kitasato
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Mizushima
authors.forename: S
authors.initials: S
authors.lastname: Kawai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone