INVOLVEMENT OF NF-KAPPA-B IN THE REGULATION OF CYCLOOXYGENASE-2 PROTEIN EXPRESSION IN LPS-STIMULATED J774 MACROPHAGES

We investigated the involvement of NF-kappa B in the regulation of COX -2 protein expression and prostaglandin production in LPS-stimulated J 774 macrophages. Incubation of J774 cells with LPS (1 mu g/ml) for 24 h caused an increase of COX-2 protein expression and accumulation of b oth PGE(2) and 6-keto-PGF(1 alpha), in the cell culture medium, Ammoni um pyrrolidinedithiocarbamate (APDC, 0.1, 1, 10 mu M) and N-alpha-p-to syl-L-lysine chloromethylketone (TLCK, 1, 10, 100 mu M),two inhibitors of NF-kappa B activation, suppressed in a concentration-dependent man ner both LPS-induced COX-2 protein expression and prostanoid generatio n, Moreover, APDC and TLCK both inhibited the LPS-induced increase of NF-kappa B DNA binding activity and prevented I kappa B-alpha degradat ion, Our results show for the first time that NF-kappa B is involved i n COX-2 protein expression in LPS-stimulated J774 macrophages and sugg est that inhibitors of NF-kappa B activation may represent a useful to ol for the pharmacological control of inflammation. (C) 1997 Federatio n of European Biochemical Societies.