Regulation of cyclooxygenase-2 expression in bovine chondrocytes in culture by interleukin 1alpha, tumor necrosis factor-alpha, glucocorticoids, and 17beta-estradiol.
OBJECTIVE
To determine the effects of interleukin 1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), dexamethasone, and 17beta-estradiol on the expression of cyclooxygenase-1 (COX-1) and COX-2 in bovine chondrocytes.


METHODS
Northern blot analysis was used to quantify COX-1 and COX-2 mRNA expression in primary cultures of bovine chondrocytes and prostaglandin production to evaluate COX activity.


RESULTS
IL-1alpha and TNF-alpha increased the expression of COX-2. This effect was independent of de novo protein synthesis and dependent on increased mRNA stability in the case of IL-1alpha. Dexamethasone inhibited the effects of both cytokines. 17beta-estradiol inhibited COX-2 mRNA expression in basal conditions, but had no effect on COX-2 expression induced by cytokines. The specific COX-2 inhibitor compound NS 398 prevented the increase in prostaglandin E2 (PGE2) production induced by the cytokines. COX-1 levels remained stable with all treatments.


CONCLUSIONS
Increase in mRNA stability is a mechanism implicated in the induction of COX-2 by some cytokines. The effects of IL-1alpha and TNF-alpha on PGE2 production are mainly due to an increase in COX-2 activity as shown by the effect of compound NS 398. 17beta-estradiol inhibits COX-2 mRNA expression in basal conditions, suggesting that estrogens could be implicated in the control of cartilage metabolism.
Morisset
S
S
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Canada.
Patry
C
C
Lora
M
M
de Brum-Fernandes
A J
AJ
D000818:Animals; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D007527:Isoenzymes; D009578:Nitrobenzenes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004958:Estradiol; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone