- 作者: Kuo-Chin Huang Ching-Wen Chen Jui-Ching Chen Wan-Wan Lin
- 作者服務機構: Department of Family Medicine, National Taiwan University Hospital, Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, statins, are potent inhibitors ofcholesterol synthesis and have wide therapeutic use incardiovascular diseases. Recent evidence, however, sug-gests that the beneficial effects of statins may extendbeyond their action on serum cholesterol levels. In thisstudy, we investigated the effects of lovastatin, pravasta-tin, atorvastatin and fluvastatin on macrophage forma-tion of nitric oxide (NO) in murine RAW 264.7 cells. Stim-ulation of macrophages with lipopolysaccharide (LIPS)and interferon-γ (IFN-γ) resulted in inducible NO syn-thase (iNOS) expression, which was accompanied by alarge amount of NO formation. At concentrations of 0.1-30μM, statins can inhibit stimuli-induced NO formationand iNOS induction to different extents. This inhibitionoccurs at the transcriptional level, and displays potencyin the order of lovastati n>atorvastatin>fluvastatin>>pravastatin. We found that LPS-induced IKB kinase andnuclear factor- B (NF- B) activation, as well as IFN-γ-induced signal transducer and activator of transcription 1(STAT1) phosphorylation, were reduced by lovastatin.Moreover, inhibition by lovastatin of NO production andKB activation was reversed by mevalonate, geranylgera-nyl pyrophosphate and farnesyl pyrophosphate. Allthese results suggest that inhibition of iNOS gene ex-pression by statins can be attributed to interference withprotein isoprenylation, which mediates both NF- B andSTAT1 activation in the upstream signaling pathways foriNOS gene transcription.
- 中文關鍵字: --
- 英文關鍵字: Inducible nitric oxide synthase. Statins. HMG-CoA reductase. NF-kB. STAT1. Macrophage