Pravastatin down-regulates inflammatory mediators in human monocytes in vitro
(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.
(Less)
- author
- Grip, Olof LU ; Janciauskiene, Sabina LU and Lindgren, Stefan LU
- organization
- publishing date
- 2000-12-20
- 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
-
- pmid:11134659
- 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
- 2024-03-03 21:58:39
@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}},
keywords = {{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}},
doi = {{10.1016/S0014-2999(00)00870-0}},
volume = {{410}},
year = {{2000}},
}