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Suppression of nuclear factor‐κB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles
Author(s) -
De Pascale Clara,
Graham Valerie,
Fowkes Robert C.,
WheelerJones Caroline P. D.,
Botham Kathleen M.
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07260.x
Subject(s) - polyunsaturated fatty acid , foam cell , macrophage , monocyte , nf κb , biochemistry , inflammation , fatty acid , iκbα , transcription factor , chemistry , biology , signal transduction , immunology , gene , in vitro
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‐κB (NF‐κB) has been implicated. In this study, the influence of CMR on the activity of NF‐κB 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‐κB activation and downregulated the expression of phospho‐p65–NF‐κB and phospho‐IκBα (pIκBα). Secretion of the inflammatory cytokines tumour necrosis factor α, interleukin‐6 and monocyte chemoattractant protein‐1, which are under NF‐κB transcriptional control, was inhibited and mRNA expression for cyclooxygenase‐2, an NF‐κB 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‐κB binding to DNA and the expression of phospho‐p65–NF‐κB and pIκB. 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‐κB activity. These findings demonstrate that CMR suppress NF‐κB 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.