Nuclear Translocation and DNA-Binding Activity of NFKB (NF-κB) after Exposure of Human Monocytes to Pulsed Ultra-wideband Electromagnetic Fields (1 kV/cm) Fails to Transactivate κB-Dependent Gene Expression

Abstract

The objective of this study was to investigate whether exposure of human monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm average peak power triggers a signaling pathway responsible for the transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of 90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250 pps. The temperature of the medium was maintained at 37 degrees C in both sham- and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in the NFKB DNA-binding activity. Since activation of NFKB was observed, the possibility of kappaB-dependent gene expression in response to exposure to the EMFs was investigated using NFKB signal-specific gene arrays. The results revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24 h postexposure, indicating that activated NFKB does not lead to the differential expression of kappaB-dependent target genes. To determine whether the absence of the kappaB-dependent gene expression was due to compromised transcriptional regulation of NFKB, the functional activity of NFKB was examined in cells transiently transfected with Mercury Pathway constructs containing 4x NFKB binding sites associated either with the luciferase reporter system or a control vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF exposure is functionally inactive. From these results, it is clear that the EMF-induced NFKB activation is only a transient response, with minimal or no downstream effect.

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“…Leszczynski et al (2004), for example, observed an increase in HSP27 phosphorylation—which can be considered an antiapoptotic event (Morimoto 1998)—and a concomitant increase in stability of stress fibers of cells and down-regulation of genes of the Fas/TNF-α apoptotic pathway. Other authors did not observe simultaneous change in gene expression and in related downstream events: Natarajan et al (2006) reported increased DNA-binding activity of NF-kappaB in human monocytes but no transactivation of kappaB-dependent gene expression after exposure to pulsed ultra-wide-band electromagnetic fields. Nikolova et al (2005) observed changes in gene expression but without detectable change in cell physiology.…”

Low‐frequency electromagnetic fields do not alter responses of inflammatory genes and proteins in human monocytes and immune cell lines

“…The cytokines IL-1b, IL-6, IL-10, and TNF-a were found unchanged in gene expression and protein production in LF EMF-exposed PBMCs [Pessina and Aldinucci, 1997;Ikeda et al, 2003] and rat and human lymphocytes [Jasti et al, 2001;Luceri et al, 2005]. NF-kB gene expression was also found unchanged in human monocytic cells in two separate studies [Miller et al, 1999;Natarajan et al, 2006]. Although the setup of the experimental and exposure conditions differed greatly from our study, most of these studies used a 50 Hz signal.…”

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“…However, caspase-9 and Apaf-1 remain unchanged in another study [47]. The tumor necrosis fac- [63] tor (TNF)-inducible protein A20 and BCL2-related factor A1 are both upregulated [59]. In other studies, deathassociated protein DAP3 is upregulated [48], but another Dap is downregulated [51].…”