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Very low density lipoprotein potentiates tumor necrosis factor-alpha expression in macrophages.

Stollenwerk, Maria LU ; Schiopu, Alexandru LU ; Nordin Fredrikson, Gunilla LU ; Dichtl, Wolfgang; Nilsson, Jan LU and Ares, Mikko LU (2005) In Atherosclerosis 179(2). p.247-254
Abstract
High levels of the triacylglycerol-rich lipoproteins, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) have been identified as independent risk factors for coronary heart disease, and inflammation is thought to contribute to atherosclerosis and its complications. To understand how dyslipidemia promotes inflammation, we have characterised the effects of VLDL treatment on production of tumor necrosis factor-α (TNF) by human monocyte-derived macrophages. VLDL strongly potentiated lipopolysaccharide (LPS)-induced expression of TNF mRNA and secretion of TNF protein. VLDL activated mitogen-activated protein kinase-ERK kinase 1/2 (MEK1/2), and potentiated LPS-induced MEK1/2 activation. The MEK1/2 inhibitor U0126... (More)
High levels of the triacylglycerol-rich lipoproteins, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) have been identified as independent risk factors for coronary heart disease, and inflammation is thought to contribute to atherosclerosis and its complications. To understand how dyslipidemia promotes inflammation, we have characterised the effects of VLDL treatment on production of tumor necrosis factor-α (TNF) by human monocyte-derived macrophages. VLDL strongly potentiated lipopolysaccharide (LPS)-induced expression of TNF mRNA and secretion of TNF protein. VLDL activated mitogen-activated protein kinase-ERK kinase 1/2 (MEK1/2), and potentiated LPS-induced MEK1/2 activation. The MEK1/2 inhibitor U0126 strongly diminished TNF expression, indicating that MEK1/2 plays a central role in the regulation of TNF expression. VLDL did not activate transcription factors NF-κB and PPAR-γ, but it activated AP-1 at least as potently as LPS, and potentiated LPS-induced activation of AP-1. The inhibitor U0126 completely prevented this potentiation. Inhibition of AP-1 by decoy oligonucleotides abolished potentiation of TNF secretion by VLDL. In conclusion, VLDL treatment potentiates TNF expression in macrophages by activation of MEK1/2 and AP-1. These findings suggest that triacylglycerol-rich lipoproteins are involved in inflammatory processes associated with atherosclerosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Inflammation, Activator protein-1, Very low density lipoprotein, Tumor necrosis factor
in
Atherosclerosis
volume
179
issue
2
pages
247 - 254
publisher
Elsevier
external identifiers
  • wos:000228108900004
  • pmid:15777538
  • scopus:14944347113
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2004.12.002
language
English
LU publication?
yes
id
a45fccb3-1575-430c-b690-4b207dd13c1e (old id 134873)
date added to LUP
2007-07-30 16:16:36
date last changed
2017-10-22 03:49:55
@article{a45fccb3-1575-430c-b690-4b207dd13c1e,
  abstract     = {High levels of the triacylglycerol-rich lipoproteins, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) have been identified as independent risk factors for coronary heart disease, and inflammation is thought to contribute to atherosclerosis and its complications. To understand how dyslipidemia promotes inflammation, we have characterised the effects of VLDL treatment on production of tumor necrosis factor-α (TNF) by human monocyte-derived macrophages. VLDL strongly potentiated lipopolysaccharide (LPS)-induced expression of TNF mRNA and secretion of TNF protein. VLDL activated mitogen-activated protein kinase-ERK kinase 1/2 (MEK1/2), and potentiated LPS-induced MEK1/2 activation. The MEK1/2 inhibitor U0126 strongly diminished TNF expression, indicating that MEK1/2 plays a central role in the regulation of TNF expression. VLDL did not activate transcription factors NF-κB and PPAR-γ, but it activated AP-1 at least as potently as LPS, and potentiated LPS-induced activation of AP-1. The inhibitor U0126 completely prevented this potentiation. Inhibition of AP-1 by decoy oligonucleotides abolished potentiation of TNF secretion by VLDL. In conclusion, VLDL treatment potentiates TNF expression in macrophages by activation of MEK1/2 and AP-1. These findings suggest that triacylglycerol-rich lipoproteins are involved in inflammatory processes associated with atherosclerosis.},
  author       = {Stollenwerk, Maria and Schiopu, Alexandru and Nordin Fredrikson, Gunilla and Dichtl, Wolfgang and Nilsson, Jan and Ares, Mikko},
  issn         = {1879-1484},
  keyword      = {Atherosclerosis,Inflammation,Activator protein-1,Very low density lipoprotein,Tumor necrosis factor},
  language     = {eng},
  number       = {2},
  pages        = {247--254},
  publisher    = {Elsevier},
  series       = {Atherosclerosis},
  title        = {Very low density lipoprotein potentiates tumor necrosis factor-alpha expression in macrophages.},
  url          = {http://dx.doi.org/10.1016/j.atherosclerosis.2004.12.002},
  volume       = {179},
  year         = {2005},
}