Morisset S, Patry C, Lora M, de Brum-Fernandes A J
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Canada.
J Rheumatol. 1998 Jun;25(6):1146-53.
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.
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.
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.
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.
确定白细胞介素1α（IL-1α）、肿瘤坏死因子-α（TNF-α）、地塞米松和17β-雌二醇对牛软骨细胞中环氧合酶-1（COX-1）和环氧合酶-2（COX-2）表达的影响。
采用Northern印迹分析法定量牛软骨细胞原代培养物中COX-1和COX-2 mRNA的表达，并通过前列腺素生成来评估COX活性。
IL-1α和TNF-α增加了COX-2的表达。这种作用与从头合成蛋白质无关，就IL-1α而言，依赖于mRNA稳定性的增加。地塞米松抑制了两种细胞因子的作用。17β-雌二醇在基础条件下抑制COX-2 mRNA表达，但对细胞因子诱导的COX-2表达没有影响。特异性COX-2抑制剂化合物NS 398可阻止细胞因子诱导的前列腺素E2（PGE2）生成增加。所有处理下COX-1水平保持稳定。
mRNA稳定性增加是某些细胞因子诱导COX-2的一种机制。如化合物NS 398的作用所示，IL-1α和TNF-α对PGE2生成的影响主要是由于COX-2活性增加。17β-雌二醇在基础条件下抑制COX-2 mRNA表达，提示雌激素可能参与软骨代谢的调控。
