Cyclolinteinone, a sesterterpene from sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase proteinexpression by blocking nuclear factor-kappa B activation in J774 macrophages

We investigated the effect of cyclolinteinone, a sesterterpene from Caribbe an sponge Cacospongia linteiformis, mis, on inducible NO synthase (iNOS) an d cyclo-oxygenase-2 (COX-?) protein expression in lipopolysaccharide (LPS)- stimulated J774 macrophages. Incubation of J774 cells with LPS (1 mu g/ml) caused an increase of both iNOS and COX-2 protein expression, which was pre vented in a concentration-dependent fashion by cyclolinteinone (12.5, 25 an d 50 mu M). Electrophoretic mobility-shift assay indicated that cyclolintei none blocked the activation of nuclear factor-kappa B (NF-KB), a transcript ion factor necessary for either iNOS or COX-2 induction. Cyclolinteinone al so blocked disappearance of I,B-cr from cytosolic fraction and nuclear tran slocation of NF-KB subunits p50 and p65. These results show that cyclolinte inone down-regulates iNOS and COX-2 protein expression by inhibiting NF-KB activation and suggest that it may represent a novel anti-inflammatory comp ound capable of controlling the excessive production of prostaglandins and nitric oxide occurring in several inflammatory diseases.