Modulation of inflammatory mediators and PPARgamma and NFkappaB expression by pravastatin in response to lipoproteins in human monocytes in vitro.

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作者：

I Zelvyte，R Dominaitiene，M Crisby，S Janciauskiene

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摘要：

Statins are inhibitors of the rate-limiting step of cellular cholesterol synthesis. In vitro and in vivo studies suggest that statins have anti-inflammatory properties independent of their cholesterol-lowering effects. These observations prompted us to examine the effects of pravastatin (50 μ M) and native or oxidized low density lipoprotein (nLDL or oxLDL) (50 μ g ml1) on primary human monocytes. We found that cells treated with pravastatin prior to nLDL and cells pre-treated with oxLDL prior to pravastatin showed increased activity of peroxisome proliferator-activated receptor gamma (PPAR γ). Treatment of cells with drug either before incubation with oxLDL or afterwards suppressed nuclear factor kappa B (NF κ B) expression and reduced uptake of125I-oxLDL by 1.7- and 1.5-fold, respectively. Pravastatin also increased PPAR γ levels and abolished NF κ B activity in non-stimulated monocytes. Statin added to monocytes prior to or after treatment with nLDL or oxLDL significantly inhibited generation of matrix metalloproteinases (MMPs), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor alpha (TNF- α). These data corroborate previous findings of the pleiotropic role of statins and also suggest the involvement of transcription factors such as PPAR γ and NFκ B in the modulation of the inflammatory processes by statins.

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关键词：

pravastatin, inflammation, lipid metabolism, pro-inflammatory molecules, PPARs

DOI：

10.1006/phrs.2001.0922

被引量：

555

年份：

2002