Prostaglandins prevent inducible nitric oxide synthase protein expression by inhibiting nuclear factor‐κB activation in J774 macrophages

FEBS Letters

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

[1] Department of Experimental Pharmacology, Via Domenico Montesano, 49, University of Naples ‘Federico II', 80131 Naples, Italy

关键词: Prostaglandin;    Inducible nitric oxide synthase;    Nuclear factor-κB;    Lipopolysaccharide;    iNOS;    inducible nitric oxide synthase;    NF-κB;    nuclear factor-κB;    LPS;    lipopolysaccharide;   

DOI  :  10.1016/S0014-5793(98)01407-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated the effect of PGE₂ and iloprost (a prostacyclin analogue) on inducible nitric oxide synthase (iNOS) protein expression and nuclear factor-κB (NF-κB) activation in lipopolysaccharide (LPS)-stimulated J774 macrophages. Incubation of J774 cells with LPS (10 μg/ml) caused an increase of iNOS protein expression which was prevented in a concentration-dependent fashion by PGE₂ (0.1, 1, 10 μM) and iloprost (0.01, 0.1, 1 μM). Electrophoretic mobility shift assay indicated that both prostanoids blocked the activation of NF-κB, a transcription factor necessary for NO synthase induction. PGE₂ and iloprost also blocked disappearance of IκB-α from cytosolic fraction and nuclear translocation of NF-κB subunits p50 and p65. These results show for the first time that PGE₂ and iloprost down-regulate iNOS protein expression by inhibiting NF-κB activation and suggest a negative feed-back mechanism that may be important for limiting excessive or prolonged NO production in pathological events.

【 授权许可】

Unknown