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Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism.

Lindholm, Marie LU and Nilsson, Jan LU (2007) In Vascular Pharmacology 46(Jul 25). p.91-96
Abstract
Statin treatment inhibits oxidized lipoprotein-induced intracellular lipid accumulation (foam cell formation) and reduces plasma levels of inflammatory markers such as interleukin-1 beta The aim of the present study was to determine if simvastatin affected lipid accumulation in macrophages incubated with aggregated low density lipoproteins (AgLDL) and whether simvastatin had a direct effect on cytokine secretion from macrophages. Simvastatin treatment did not inhibit AgLDL-induced macrophage lipid accumulation, but significantly increased the secretion of IL-1 beta and IL-8 from macrophages, whilst inhibiting the secretion of tumor necrosis factor-alpha (TNF-alpha) and having no significant effect on IL-6 secretion. Increased macrophage... (More)
Statin treatment inhibits oxidized lipoprotein-induced intracellular lipid accumulation (foam cell formation) and reduces plasma levels of inflammatory markers such as interleukin-1 beta The aim of the present study was to determine if simvastatin affected lipid accumulation in macrophages incubated with aggregated low density lipoproteins (AgLDL) and whether simvastatin had a direct effect on cytokine secretion from macrophages. Simvastatin treatment did not inhibit AgLDL-induced macrophage lipid accumulation, but significantly increased the secretion of IL-1 beta and IL-8 from macrophages, whilst inhibiting the secretion of tumor necrosis factor-alpha (TNF-alpha) and having no significant effect on IL-6 secretion. Increased macrophage lipid content did not block statin-induced and IL-8 secretion. Simvastatin-stimulated IL-1 beta secretion from macrophages was inhibited by isoprenoids. We therefore hypothesized that simvastatin stimulated IL-1 beta secretion by affecting isoprenylation-dependent signaling pathways. Another possible mechanism for affecting such signaling is to impair isoprenoid transfer protein activity with specific inhibitors such as GGT1-297 and FTInhI. This treatment resulted in strong stimulation of IL-1 beta secretion that was further enhanced when exogenous IL-1 beta was present at the beginning of treatment. These data suggest an isoprenylation-dependent negative-feedback loop for macrophage IL-1 beta secretion that is inhibited by statin treatment. (c) 2006 Elsevier Inc. All rights reserved. (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
lipid, statin, interleukin, isoprenylation, macrophage
in
Vascular Pharmacology
volume
46
issue
Jul 25
pages
91 - 96
publisher
Elsevier
external identifiers
  • wos:000243657300003
  • scopus:33845604074
ISSN
1537-1891
DOI
10.1016/j.vph.2006.07.001
language
English
LU publication?
yes
id
3dd8d3ea-068b-43e5-8e3b-b294568261b9 (old id 161355)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16942919&dopt=Abstract
date added to LUP
2007-07-25 15:25:56
date last changed
2017-01-01 04:35:30
@article{3dd8d3ea-068b-43e5-8e3b-b294568261b9,
  abstract     = {Statin treatment inhibits oxidized lipoprotein-induced intracellular lipid accumulation (foam cell formation) and reduces plasma levels of inflammatory markers such as interleukin-1 beta The aim of the present study was to determine if simvastatin affected lipid accumulation in macrophages incubated with aggregated low density lipoproteins (AgLDL) and whether simvastatin had a direct effect on cytokine secretion from macrophages. Simvastatin treatment did not inhibit AgLDL-induced macrophage lipid accumulation, but significantly increased the secretion of IL-1 beta and IL-8 from macrophages, whilst inhibiting the secretion of tumor necrosis factor-alpha (TNF-alpha) and having no significant effect on IL-6 secretion. Increased macrophage lipid content did not block statin-induced and IL-8 secretion. Simvastatin-stimulated IL-1 beta secretion from macrophages was inhibited by isoprenoids. We therefore hypothesized that simvastatin stimulated IL-1 beta secretion by affecting isoprenylation-dependent signaling pathways. Another possible mechanism for affecting such signaling is to impair isoprenoid transfer protein activity with specific inhibitors such as GGT1-297 and FTInhI. This treatment resulted in strong stimulation of IL-1 beta secretion that was further enhanced when exogenous IL-1 beta was present at the beginning of treatment. These data suggest an isoprenylation-dependent negative-feedback loop for macrophage IL-1 beta secretion that is inhibited by statin treatment. (c) 2006 Elsevier Inc. All rights reserved.},
  author       = {Lindholm, Marie and Nilsson, Jan},
  issn         = {1537-1891},
  keyword      = {lipid,statin,interleukin,isoprenylation,macrophage},
  language     = {eng},
  number       = {Jul 25},
  pages        = {91--96},
  publisher    = {Elsevier},
  series       = {Vascular Pharmacology},
  title        = {Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism.},
  url          = {http://dx.doi.org/10.1016/j.vph.2006.07.001},
  volume       = {46},
  year         = {2007},
}