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

Zelvyté, Inga LU ; Dominaitiene, Ruta; Crisby, Milita and Janciauskiene, Sabina LU (2002) In Pharmacological Research 45(2). p.147-154
Abstract
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 mgr; M) and native or oxidized low density lipoprotein (nLDL or oxLDL) (50 mgr; g ml(minus sign1)) 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 gamma). Treatment of cells with drug either before incubation with oxLDL or afterwards suppressed nuclear factor kappa B (NF kappa B)... (More)
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 mgr; M) and native or oxidized low density lipoprotein (nLDL or oxLDL) (50 mgr; g ml(minus sign1)) 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 gamma). Treatment of cells with drug either before incubation with oxLDL or afterwards suppressed nuclear factor kappa B (NF kappa B) expression and reduced uptake of(125)I-oxLDL by 1.7- and 1.5-fold, respectively. Pravastatin also increased PPAR gamma levels and abolished NF kappa 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- alpha). These data corroborate previous findings of the pleiotropic role of statins and also suggest the involvement of transcription factors such as PPAR gamma and NF kappa B in the modulation of the inflammatory processes by statins. Copyright 2002 Elsevier Science Ltd. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lipoproteins, monocytes, Monocyte Chemoattractant Protein-1, NF kappa B, pravastatin
in
Pharmacological Research
volume
45
issue
2
pages
147 - 154
publisher
Academic Press
external identifiers
  • wos:000174516100012
  • pmid:11846628
  • scopus:0036445650
ISSN
1096-1186
DOI
10.1006/phrs.2001.0922
language
English
LU publication?
yes
id
53dcbf95-1a5e-40ec-aa32-46cfa9d34397 (old id 106017)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11846628&dopt=Abstract
date added to LUP
2007-07-30 13:13:08
date last changed
2017-08-27 04:13:04
@article{53dcbf95-1a5e-40ec-aa32-46cfa9d34397,
  abstract     = {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 mgr; M) and native or oxidized low density lipoprotein (nLDL or oxLDL) (50 mgr; g ml(minus sign1)) 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 gamma). Treatment of cells with drug either before incubation with oxLDL or afterwards suppressed nuclear factor kappa B (NF kappa B) expression and reduced uptake of(125)I-oxLDL by 1.7- and 1.5-fold, respectively. Pravastatin also increased PPAR gamma levels and abolished NF kappa 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- alpha). These data corroborate previous findings of the pleiotropic role of statins and also suggest the involvement of transcription factors such as PPAR gamma and NF kappa B in the modulation of the inflammatory processes by statins. Copyright 2002 Elsevier Science Ltd.},
  author       = {Zelvyté, Inga and Dominaitiene, Ruta and Crisby, Milita and Janciauskiene, Sabina},
  issn         = {1096-1186},
  keyword      = {lipoproteins,monocytes,Monocyte Chemoattractant Protein-1,NF kappa B,pravastatin},
  language     = {eng},
  number       = {2},
  pages        = {147--154},
  publisher    = {Academic Press},
  series       = {Pharmacological Research},
  title        = {Modulation of inflammatory mediators and ppargammaand nfkappab expression by pravastatin in response to lipoproteins in human monocytes in vitro.},
  url          = {http://dx.doi.org/10.1006/phrs.2001.0922},
  volume       = {45},
  year         = {2002},
}