Research article summary (published 31 Aug 2009):

Suppression of nuclear factor-kappaB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles.

Full Abstract

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated. In this study, the influence of CMR on the activity of NF-kappaB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs). Incubation of THP-1 macrophages with CRLPs caused decreased NF-kappaB activation and downregulated the expression of phospho-p65-NF-kappaB and phospho-IkappaBalpha (pIkappaBalpha). Secretion of the inflammatory cytokines tumour necrosis factor alpha, interleukin-6 and monocyte chemoattractant protein-1, which are under NF-kappaB transcriptional control, was inhibited and mRNA expression for cyclooxygenase-2, an NF-kappaB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF-kappaB binding to DNA and the expression of phospho-p65-NF-kappaB and pIkappaB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF-kappaB activity. These findings demonstrate that CMR suppress NF-kappaB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids.

Author information

Author/s: De Pascale, Clara (C); Graham, Valerie (V); Fowkes, Robert C (RC); Wheeler-Jones, Caroline P D (CP); Botham, Kathleen M (KM);

Affiliation: Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.

Grants: (Agency:British Heart Foundation)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The FEBS journal (FEBS J), published in England. (Language: eng)

Reference: 2009-Oct; vol 276 (issue 19) : pp 5689-702

Dates: Created 2009/09/22; Completed 2009/10/22;

PMID: 19725874, status: MEDLINE (last retrieval date: 10/22/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Base Sequence Biological Transport, Active - drug effects Cell Line Chemokines - biosynthesis; genetics Cholesterol - metabolism Chylomicron Remnants - chemistry; pharmacology Cyclooxygenase 2 - genetics Cytokines - biosynthesis; genetics DNA - metabolism DNA Primers - genetics Down-Regulation - drug effects Fatty Acids - analysis; pharmacology

Fatty Acids - analysis; pharmacology Fish Oils - pharmacology Humans I-kappa B Proteins - metabolism Inflammation - prevention & control Macrophages - drug effects; metabolism NF-kappa B - metabolism Phosphorylation Plant Oils - pharmacology RNA, Messenger - genetics; metabolism Transcription Factor RelA - metabolism Triglycerides - analysis; pharmacology

Associated Chemicals: Chemokines (0) ; Chylomicron Remnants (0) ; Cytokines (0) ; DNA Primers (0) ; Fatty Acids (0) ; Fish Oils (0) ; I-kappa B Proteins (0) ; NF-kappa B (0) ; Plant Oils (0) ; RNA, Messenger (0) ; Transcription Factor RelA (0) ; Triglycerides (0) ; NF-kappaB inhibitor alpha (139874-52-5) ; trilinolein (537-40-6) ; Cholesterol (57-88-5) ; DNA (9007-49-2) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1)

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