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Pravastatin down-regulates inflammatory mediators in human monocytes in vitro

Grip, Olof LU ; Janciauskiene, Sabina LU and Lindgren, Stefan LU (2000) In European Journal of Pharmacology 410(1). p.83-92
Abstract

There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression... (More)

There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression (up to 15-fold), reduction of tumour necrosis factor alpha (TNF-α) levels (up to 2.4-fold) and a total loss of metalloproteinase-9 activity in stimulated cells. Pravastatin at concentrations of 5, 100 and 500 μM caused an inhibition of TNF-α-induced cellular oxygen consumption from 2.4- to 5.5-fold. These data extend the findings of potential anti-inflammatory actions of statins and also suggest the possibility for pravastatin use in a broader spectrum of inflammatory situations.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Inflammation, Lipid metabolism, Monocyte, Pravastatin, Pro-inflammatory molecule
in
European Journal of Pharmacology
volume
410
issue
1
pages
83 - 92
publisher
Elsevier
external identifiers
  • scopus:0034694774
ISSN
0014-2999
DOI
10.1016/S0014-2999(00)00870-0
language
English
LU publication?
yes
id
ebe4cafb-31b8-4c91-992c-1c4da0015e9b
date added to LUP
2019-08-07 13:29:56
date last changed
2019-09-11 04:22:03
@article{ebe4cafb-31b8-4c91-992c-1c4da0015e9b,
  abstract     = {<p>There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression (up to 15-fold), reduction of tumour necrosis factor alpha (TNF-α) levels (up to 2.4-fold) and a total loss of metalloproteinase-9 activity in stimulated cells. Pravastatin at concentrations of 5, 100 and 500 μM caused an inhibition of TNF-α-induced cellular oxygen consumption from 2.4- to 5.5-fold. These data extend the findings of potential anti-inflammatory actions of statins and also suggest the possibility for pravastatin use in a broader spectrum of inflammatory situations.</p>},
  author       = {Grip, Olof and Janciauskiene, Sabina and Lindgren, Stefan},
  issn         = {0014-2999},
  keyword      = {Inflammation,Lipid metabolism,Monocyte,Pravastatin,Pro-inflammatory molecule},
  language     = {eng},
  month        = {12},
  number       = {1},
  pages        = {83--92},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Pravastatin down-regulates inflammatory mediators in human monocytes in vitro},
  url          = {http://dx.doi.org/10.1016/S0014-2999(00)00870-0},
  volume       = {410},
  year         = {2000},
}