Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism.
Författare
Summary, in English
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.
Publiceringsår
2007
Språk
Engelska
Sidor
91-96
Publikation/Tidskrift/Serie
Vascular Pharmacology
Volym
46
Issue
Jul 25
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cardiac and Cardiovascular Systems
Nyckelord
- lipid
- statin
- interleukin
- isoprenylation
- macrophage
Status
Published
Forskningsgrupp
- Cardiovascular Research - Immunity and Atherosclerosis
ISBN/ISSN/Övrigt
- ISSN: 1537-1891