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.
These findings demonstrate that TRLs derived from olive oil influence inflammatory processes in macrophages and suggest that oleanolic acid may have beneficial effects.
Jejunal fluid absorption in vivo was reduced by distension and by hydrostatic pressure and further declined on adding E. coli STa enterotoxin but no net fluid secretion was detected. Luminal atropine reduced pressure mediated reductions in fluid absorption to normal values but intravenous hexamethonium was without effect. A neural component to inhibition of absorption by pressure (though not stretch) may be mediated by axon reflexes within cholinergic neurons. Perfusion of cholinergic compounds also reduced net fluid absorption but did not cause secretion. In order to show that these actions were not secretory processes stimulated by cholinergic compounds that offset normal rates of absorption, these compounds were tested for their ability to cause net secretion in loops that were perfused with solutions in which choline substituted for sodium ion. In addition, these perfusates additionally contained E. coli STa enterotoxin or EIPA (ethyl-isopropylamiloride) to minimize absorption. In these circumstances, where it might be expected to do so if it Original Research Article
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