Very low density lipoprotein potentiates tumor necrosis factor-alpha expression in macrophages.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/134873
- author
- Stollenwerk, Maria LU ; Schiopu, Alexandru LU ; Nordin Fredrikson, Gunilla LU ; Dichtl, Wolfgang ; Nilsson, Jan LU and Ares, Mikko LU
- organization
- publishing date
- 2005
- 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
- pmid:15777538
- 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
- 2016-04-01 12:17:22
- date last changed
- 2022-01-27 01:34:04
@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}},
keywords = {{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}},
doi = {{10.1016/j.atherosclerosis.2004.12.002}},
volume = {{179}},
year = {{2005}},
}