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

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.

MEG-measured visually induced gamma-band oscillations in chronic schizophrenia: Evidence for impaired generation of rhythmic activity in ventral stream regions

Background: Gamma-band oscillations are prominently impaired in schizophrenia, but the nature of the deficit and relationship to perceptual processes is unclear. Methods: 16 patients with chronic schizophrenia (ScZ) and 16 age-matched healthy controls completed a visual paradigm while magnetoencephalographic (MEG) data was recorded. Participants had to detect randomly occurring stimulus acceleration while viewing a concentric moving grating. MEG data were analyzed for spectral power (1-100 Hz) at sensorand source-level to examine the brain regions involved in aberrant rhythmic activity, and for contribution of differences in baseline activity towards the generation of low- and highfrequency power. Results: Our data show reduced gamma-band power at sensor level in schizophrenia patients during stimulus processing while alpha-band and baseline spectrum were intact. Differences in oscillatory activity correlated with reduced behavioral detection rates in the schizophrenia group and higher scores on the “Cognitive Factor” of the Positive and Negative Syndrome Scale. Source reconstruction revealed that extra-striate (fusiform/lingual gyrus), but not striate (cuneus), visual cortices contributed towards the reduced activity observed at sensorlevel in ScZ patients. Importantly, differences in stimulus-related activity were not due to differences in baseline activity. Conclusions: Our findings highlight that MEG-measured high-frequency oscillations during visual processing can be robustly identified in ScZ. Our data further suggest impairments that involve dysfunctions in ventral stream processing and a failure to increase gamma-band activity in a task-context. Implications of these findings are discussed in the context of current theories of cortical-subcortical circuit dysfunctions and perceptual processing in ScZ.