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

Stollenwerk, Maria M (author)
Schiopu, A (author)
Nordin Fredrikson, Gunilla (author)
Malmö högskola,Fakulteten för hälsa och samhälle (HS)
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Dichtl, W (author)
Nilsson, J (author)
Ares, Mikko PS (author)
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 (creator_code:org_t)
Elsevier Ireland Ltd. 2005
2005
English.
In: Atherosclerosis. - : Elsevier Ireland Ltd.. - 0021-9150 .- 1879-1484. ; 179:2, s. 247-254
  • Journal article (peer-reviewed)
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

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Stollenwerk, Mar ...
Schiopu, A
Nordin Fredrikso ...
Dichtl, W
Nilsson, J
Ares, Mikko PS
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Medical Biotechn ...
and Biomedical Labor ...
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Atherosclerosis
By the university
Malmö University

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