Involvement of NF‐κB in the regulation of cyclooxygenase‐2 protein expression in LPS‐stimulated J774 macrophages

FEBS Letters

Di Rosa, Massimo¹  Iuvone, Teresa¹  Rombolà, Laura¹  Carnuccio, Rosa¹  Sautebin, Lidia¹  D'Acquisto, Fulvio¹ 

[1] Department of Experimental Pharmacology, Via Domenico Montesano, 49, Faculty of Pharmacy, University of Naples `Federico II', Naples, Italy

关键词: COX-2;    Prostaglandin;    NF-κB;    Tosyl-lysine chloromethylketone;    Ammonium pyrrolidinedithiocarbamate;   

DOI  :  10.1016/S0014-5793(97)01377-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated the involvement of NF-κB in the regulation of COX-2 protein expression and prostaglandin production in LPS-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 μg/ml) for 24 h caused an increase of COX-2 protein expression and accumulation of both PGE₂ and 6-keto-PGF_1α in the cell culture medium. Ammonium pyrrolidinedithiocarbamate (APDC, 0.1, 1, 10 μM) and N-α-p-tosyl-l-lysine chloromethylketone (TLCK, 1, 10, 100 μM), two inhibitors of NF-κB 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-κB DNA binding activity and prevented IκB-α degradation. Our results show for the first time that NF-κB is involved in COX-2 protein expression in LPS-stimulated J774 macrophages and suggest that inhibitors of NF-κB activation may represent a useful tool for the pharmacological control of inflammation.

【 授权许可】

Unknown