Involvement of NF-kappa B in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages
Involvement of NF-kappa B in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages
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DOI：
10.1016/s0014-5793(97)01377-x
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发表时间：
1997-11-24
期刊：
影响因子：
3.5
通讯作者：
Carnuccio, R
中科院分区：
文献类型：
--
作者：
DAcquisto, F;Iuvone, T;Carnuccio, R
我们研究了NF-κ B B参与LPS刺激的J774巨噬细胞中考克斯-2蛋白表达和前列腺素产生的调节。用LPS孵育J774细胞（1 μ g/ml）作用24小时，导致细胞培养基中考克斯-2蛋白表达增加，PGE（2）和6-酮-PGF（1 α）积聚，（APDC，0.1、1、10 μ M）和N-α-对甲苯磺酰基-L-赖氨酸氯甲基酮（TLCK，1，10，100 μ M），两种NF-κ B活化抑制剂，以浓度依赖性方式抑制LPS诱导的考克斯-2蛋白表达和前列腺素类生成，此外，APDC和TLCK均抑制LPS诱导的NF-κ B DNA结合活性的增加，并阻止I κ B-α降解。我们的研究结果首次表明，NF-κ B参与LPS刺激的J774巨噬细胞中考克斯-2蛋白的表达，并表明NF-κ B激活的抑制剂可能代表一个有用的工具，用于药理学控制炎症。(C)1997年欧洲生物化学学会联合会。
We investigated the involvement of NF-kappa B in the regulation of COX-2 protein expression and prostaglandin production in LPS-stimulated J774 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 both PGE(2) and 6-keto-PGF(1 alpha), in the cell culture medium, Ammonium pyrrolidinedithiocarbamate (APDC, 0.1, 1, 10 mu M) and N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK, 1, 10, 100 mu M),two inhibitors of NF-kappa B activation, suppressed in a concentration-dependent manner both LPS-induced COX-2 protein expression and prostanoid generation, Moreover, APDC and TLCK both inhibited the LPS-induced increase of NF-kappa B DNA binding activity and prevented I kappa B-alpha degradation, Our results show for the first time that NF-kappa B is involved in COX-2 protein expression in LPS-stimulated J774 macrophages and suggest that inhibitors of NF-kappa B activation may represent a useful tool for the pharmacological control of inflammation. (C) 1997 Federation of European Biochemical Societies.