Barrios-Rodiles M, Keller K, Belley A, Chadee K
Institute of Parasitology of McGill University, Quebec, Canada.
Biochem Biophys Res Commun. 1996 Aug 23;225(3):896-900. doi: 10.1006/bbrc.1996.1269.
At present it is unclear whether nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit cyclooxygenase (COX) gene expression. In some cells that express COX-2, NSAIDs can inhibit enzymatic activity and gene expression. In this study we evaluated the effect of several NSAIDs on COX-1 and COX-2 mRNA, protein expression and PGE2 production in PMA-differentiated THP-1 and U937 human macrophages stimulated with LPS. Macrophages pre-treated with acetylsalicylic acid, indomethacin, naproxen or NS-398 and stimulated with LPS showed a marked inhibition on PGE2 production but not on COX-1 or COX-2 mRNA and protein expression. Furthermore, COX-2 mRNA levels induced by LPS were transient (peak 3-4 h), suggesting that PGE2 was unable to regulate COX-2 expression in an autocrine manner. These results demonstrate that NSAID's action in human macrophages is not directed towards the transcription or translation of the COX genes but only to the enzymatic activity of the proteins.
目前尚不清楚非甾体抗炎药（NSAIDs）是否能抑制环氧化酶（COX）基因表达。在一些表达COX-2的细胞中，NSAIDs能抑制酶活性和基因表达。在本研究中，我们评估了几种NSAIDs对经佛波酯（PMA）分化的THP-1和U937人巨噬细胞中COX-1和COX-2 mRNA、蛋白表达以及脂多糖（LPS）刺激后前列腺素E2（PGE2）产生的影响。用乙酰水杨酸、吲哚美辛、萘普生或NS-398预处理并经LPS刺激的巨噬细胞，PGE2产生受到显著抑制，但COX-1或COX-2 mRNA及蛋白表达未受影响。此外，LPS诱导的COX-2 mRNA水平是短暂的（峰值在3 - 4小时），这表明PGE2无法以自分泌方式调节COX-2表达。这些结果表明，NSAIDs在人巨噬细胞中的作用并非针对COX基因的转录或翻译，而仅针对蛋白的酶活性。
