These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status. This trial was registered at clinicaltrials.gov as NCT00124852.

Background: Peripheral blood mononuclear cells (PBMCs) are the only readily available cells in healthy humans. Various studies showed disease-characteristic gene expression patterns in PBMCs. However, little is known of nutritional effects on PBMC gene expression patterns. Fatty acids are nutrients that regulate gene expression by activating the nuclear receptor peroxisome proliferatoractivated receptor ␣ (PPAR␣). PBMCs express PPAR␣, making these cells interesting to study FA-dependent gene expression. Objective: The aim of this study was to elucidate whether PBMC gene expression profiles also reflect nutrition-related metabolic changes. Furthermore, we focused on the specific role of PPAR␣ in regulation of PBMC gene expression during fasting, when plasma free fatty acids are elevated. Design: Four healthy male volunteers fasted for 48 h. PBMC RNA was hybridized on Affymetrix whole genome microarrays. To elucidate the role of PPAR␣, PBMCs of 9 blood donors were incubated with the specific PPAR␣ ligand Wy14643. Results: After 24 and 48 h of fasting, 1200 and 1386 genes were changed 1.4-fold, respectively. Many of those genes were involved in fatty acid ␤-oxidation and are known PPAR␣ target genes. Incubation of PBMCs with Wy14643 resulted in up-regulation of genes that were also up-regulated during fasting. Conclusions: We conclude that PBMC gene expression profiles reflect nutrition-related metabolic changes such as fasting and that part of the fasting-induced changes are likely regulated by PPAR␣.Am J Clin Nutr 2007;86:1515-23.

This study showed that PBMCs can reveal fatty acid-specific gene expression profiles in young healthy men after the consumption of different fatty acids, as evidenced by the opposite effects of PUFA and SFA intakes on the expression of genes involved in liver X receptor signaling. This trial was registered at www.clinicaltrials.gov as NCT01000194.

BackgroundPeripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) has a functional role in human PBMCs during fasting. However, the extent of the role of PPARα in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPARα ligand WY14,643.ResultsIncubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPARα activation between six healthy human blood donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in β-oxidation were up-regulated upon activation of PPARα with WY14,643, and genes in several amino acid metabolism pathways were down-regulated.ConclusionThis study shows that PPARα in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We showed that PBMCs are a suitable model to study changes in PPARα activation in healthy humans.

The effects of low frequency electromagnetic fields (LF EMF) on human health are the subject of on-going research and serious public concern. These fields potentially elicit small effects that have been proposed to have consequences, either positive or negative, for biological systems. To reveal potentially weak but biologically relevant effects, we chose to extensively examine exposure of immune cells to two different signals, namely a complex multiple waveform field, and a 50 Hz sine wave. These immune cells are highly responsive and, in vivo, modulation of cytokine expression responses can result in systemic health effects. Using time course experiments, we determined kinetics of cytokine and other inflammation-related genes in a human monocytic leukemia cell line, THP-1, and primary monocytes and macrophages. Moreover, cytokine protein levels in THP-1 monocytes were determined. Exposure to either of the two signals did not result in a significant effect on gene and protein expression in the studied immune cells. Also, additional experiments using non-immune cells showed no effects of the signals on cytokine gene expression. We therefore conclude that these LF EMF exposure conditions are not expected to significantly modulate innate immune signaling. Bioelectromagnetics ß 2011 Wiley-Liss, Inc.

The effects of extremely low frequency electromagnetic fields (ELF-EMF) on human health remain unclear. It has been reported that ELF-EMF may modulate the innate immune response to microorganisms in animal models and mammalian cell-lines. With the recently gained insight in innate immune signaling and the discovery of pattern recognition, we aim to study whether ELF-EMF modulates innate inflammatory signaling pathways. We used human peripheral blood mononuclear cells (PBMCs), isolated from blood from healthy volunteers, which we stimulated with specific TLR2 and TLR4 ligands, and with several microorganisms. The cells were subsequently exposed in B(dc)=3 μT to a highly controlled and standardized ELF-EMF signal (20-5000Hz, B(ac)=5 μT, 30 min) and cytokine production was measured at different time points after stimulation. No significant difference in immune response, as reflected by IL-1β, IL-6, TNFα, IL-8 and IL-10 production, could be detected after stimulation with LPS (TLR4 ligand), Pam3Cys (TLR2 ligand) or a panel of heat killed microorganisms: Mycobacterium tuberculosis, Salmonella typhimurium, Candida albicans, Aspergillus fumigatus and Staphylococcus aureus (multiple TLR ligands). We therefore conclude that under our experimental conditions, ELF-EMF does not modulate the innate immune response of human primary cells after TLR stimulation in vitro.

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