Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism.
(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:
https://lup.lub.lu.se/record/161355
- author
- Lindholm, Marie LU and Nilsson, Jan LU
- organization
- publishing date
- 2007
- 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
- 2016-04-01 11:50:22
- date last changed
- 2022-04-20 22:36:12
@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}},
keywords = {{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}},
doi = {{10.1016/j.vph.2006.07.001}},
volume = {{46}},
year = {{2007}},
}