The molecular mechanism of inhibition of interleukin-1beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract.
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.
Maekawa
K
K
Institute of Medical Science, St Marianna University School of Medicine, Miyamae, Kawasaki, Japan.
Yoshikawa
N
N
Du
J
J
Nishida
S
S
Kitasato
H
H
Okamoto
K
K
Tanaka
H
H
Mizushima
Y
Y
Kawai
S
S
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
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