D'acquisto F, Lanzotti V, Carnuccio R
Department of Experimental Pharmacology, Via Domenico Montesano, 49, University of Naples 'Federico II', 80131, Naples, Italy.
Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):793-8.
We investigated the effect of cyclolinteinone, a sesterterpene from Caribbean sponge Cacospongia linteiformis, on inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2) protein expression in lipopolysaccharide (LPS)-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 microgram/ml) caused an increase of both iNOS and COX-2 protein expression, which was prevented in a concentration-dependent fashion by cyclolinteinone (12.5, 25 and 50 microM). Electrophoretic mobility-shift assay indicated that cyclolinteinone blocked the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor necessary for either iNOS or COX-2 induction. Cyclolinteinone also blocked disappearance of I(kappa)B-alpha from cytosolic fraction and nuclear translocation of NF-kappaB subunits p50 and p65. These results show that cyclolinteinone down-regulates iNOS and COX-2 protein expression by inhibiting NF-kappaB activation and suggest that it may represent a novel anti-inflammatory compound capable of controlling the excessive production of prostaglandins and nitric oxide occurring in several inflammatory diseases.
我们研究了来自加勒比海绵线形钙海绵（Cacospongia linteiformis）的倍半萜环林西酮对脂多糖（LPS）刺激的J774巨噬细胞中诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白表达的影响。用LPS（1微克/毫升）孵育J774细胞会导致iNOS和COX-2蛋白表达增加，而环林西酮（12.5、25和50微摩尔）能以浓度依赖的方式抑制这种增加。电泳迁移率变动分析表明，环林西酮可阻断核因子-κB（NF-κB）的激活，NF-κB是诱导iNOS或COX-2所必需的转录因子。环林西酮还可阻断IκB-α从胞质组分中的消失以及NF-κB亚基p50和p65的核转位。这些结果表明，环林西酮通过抑制NF-κB激活下调iNOS和COX-2蛋白表达，并提示它可能是一种新型抗炎化合物，能够控制几种炎症性疾病中发生的前列腺素和一氧化氮的过度产生。
