Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: Possible immune cell activation

Introduction: Salt Sensitivity (SS) of blood pressure (BP) is an independent predictor of death due to cardiovascular disease, but its pathogenesis is poorly understood. Sodium (Na + ) is stored in the skin and muscle interstitium. This hyperosmolar Na + activates monocytes in vitro via oxidative stress with generation of isolevuglandin (isoLG) protein adducts that are immunogenic and activate the adaptive immune system. Methods: Five subjects with essential hypertension discontinued all anti-hypertensive therapy for two weeks before the study. SS was assessed by an inpatient protocol of salt loading (460 mmoL/24h) and salt depletion (10 mmoL/24h, plus furosemide 40 mg x 3). Muscle and skin Na + contents were measured at baseline (BA) by 23 Sodium magnetic resonance imaging ( 23 NaMRI). Urine and serum electrolytes, glomerular filtration rate and the % CD14 + monocytes containing isoLG adducts using flow cytometry were obtained at BA, after salt-loading (HI) and after salt-depletion (LO). All continuous data are displayed as median (interquartile range). Spearman’s correlation was used to test associations. Results: Median age was 54 years (44-55), 60% of subjects were female, screening systolic BP (SBP) was 140 mmHg (134-148), diastolic BP was 88 mmHg (84-99) and BMI was 35 kg/m 2 (30-39). SBP response to salt-depletion (salt-sensitivity index, SSI) varied from -13.8 to +1.8 mmHg. %isoLG + CD14 + cells were 48 (27-65) at BA, 55 (31-56) at HI, and 70 (33-72) at LO (p=0.594, by the Kruskal-Wallis test). The correlation between SSI and delta (Δ) %isoLG LO minus HI, was 0.86, [95% confidence interval (CI), -0.07-0.99] which may suggest conclusively as we gather more data that the greater the SSI, the larger the decrease in isoLGs by salt depletion. Muscle Na + content correlated with 24h urine Na + (BA) (r=0.90, 95% CI, 0.11-0.99), however, the correlation with BP, SSI or isoLGs was inconclusive, potentially due to the small sample size. Skin Na + content correlated with baseline %CD14IsoLG + (r=0.91; 95% CI, 0.12-0.99). Conclusions: Na + intake is a component of the determinants of muscle Na + . Skin Na + is associated with increased isoLGs in monocytes, a marker of immune cell activation. Variability in ΔCD14isoLG may serve as a biomarker for SS of BP in humans.

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Human Gingival Fibroblasts Exposed to Extremely Low-Frequency Electromagnetic Fields: In Vitro Model of Wound-Healing Improvement

International Journal of Molecular Sciences ◽

10.3390/ijms20092108 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2108 ◽

Cited By ~ 3

Author(s):

Erica Costantini ◽

Bruna Sinjari ◽

Chiara D’Angelo ◽

Giovanna Murmura ◽

Marcella Reale ◽

...

Keyword(s):

Wound Healing ◽

Electromagnetic Field ◽

Electromagnetic Fields ◽

Wound Repair ◽

Healing Process ◽

Low Frequency ◽

Gingival Fibroblasts ◽

Field Exposure ◽

Extremely Low Frequency

Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and heme oxygenase 1 (HO-1) are involved in wound healing and tissue regeneration, favoring fibroblast proliferation, chemotaxis, and activation. Our results show that the exposure to each type of electromagnetic field increases the early expression of IL-6, TGF-β, and iNOS, driving a shift from an inflammatory to a proliferative phase of wound repair. Additionally, a later induction of MMP-2, MCP-1, and HO-1 was observed after electromagnetic field exposure, which quickened the wound-healing process. Moreover, electromagnetic field exposure influenced the proliferation, migration, and metabolism of human gingival fibroblasts compared to sham-exposed cells. This study suggests that exposure to SEMF and PEMF could be an interesting new non-invasive treatment option for wound healing. However, additional studies are needed to elucidate the best exposure conditions to provide the desired in vivo treatment efficacy.

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Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies

Journal of Experimental Medicine ◽

10.1084/jem.20181624 ◽

2019 ◽

Vol 216 (2) ◽

pp. 304-316 ◽

Cited By ~ 21

Author(s):

Ivan Kosik ◽

Davide Angeletti ◽

James S. Gibbs ◽

Matthew Angel ◽

Kazuyo Takeda ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Influenza A ◽

Cell Activation ◽

Immune Cell ◽

Broadly Neutralizing Antibodies ◽

Neutralization Activity ◽

Immune Cell Activation ◽

Influenza Virus Hemagglutinin ◽

Infected Cells

Broadly neutralizing antibodies (Abs) that bind the influenza virus hemagglutinin (HA) stem may enable universal influenza vaccination. Here, we show that anti-stem Abs sterically inhibit viral neuraminidase (NA) activity against large substrates, with activity inversely proportional to the length of the fibrous NA stalk that supports the enzymatic domain. By modulating NA stalk length in recombinant IAVs, we show that anti-stem Abs inhibit virus release from infected cells by blocking NA, accounting for their in vitro neutralization activity. NA inhibition contributes to anti-stem Ab protection in influenza-infected mice, likely due at least in part to NA-mediated inhibition of FcγR-dependent activation of innate immune cells by Ab bound to virions. Food and Drug Administration–approved NA inhibitors enhance anti-stem–based Fc-dependent immune cell activation, raising the possibility of therapeutic synergy between NA inhibitors and anti-stem mAb treatment in humans.

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Induction of Cell Activation Processes by Low Frequency Electromagnetic Fields

The Scientific World JOURNAL ◽

10.1100/tsw.2004.174 ◽

2004 ◽

Vol 4 ◽

pp. 4-22 ◽

Cited By ~ 33

Author(s):

Myrtill Simkó

Keyword(s):

Electromagnetic Fields ◽

Cellular Response ◽

Cell Activation ◽

Childhood Leukemia ◽

Mechanistic Model ◽

Cell Cycle Control ◽

Low Frequency ◽

Cellular Systems ◽

Increased Risk

Electromagnetic fields (EMF) such as those from electric power transmission and distribution lines (50/60 Hz) have been associated with increased risk of childhood leukemia, cancer of the nervous system, and lymphomas. Severalin vitrostudies on EMF effects were performed to clarify the existing controversies, define the risks, and determine the possible mechanisms of adverse effects. In some of these reports, the effects were related to other mechanisms of carcinogenesis. Modification in cell proliferation was observed after EMF exposure and a few reports on cytotoxic effects have also been published. This limited review gives an overview of the current results of scientific research regardingin vitrostudies on the effects of power line frequency EMF, but also cell biological mechanisms and their potential involvement in genotoxicity and cytotoxicity are discussed. Cell cycle control and signal transduction processes are included to elucidate the biochemical background of possible interactions. Exposure to EMF has been also linked to the incidence of leukemia and other tumors in some epidemiological studies and is considered as “possibly carcinogenic to humans”, but there is no well-established biological mechanism that explains such a relation. Furthermore, EMF is also shown as a stimulus for immune relevant cells (e.g., macrophages) to release free radicals. It is known that chronic activation of macrophages is associated with the onset of phagocytosis and leads to increased formation of reactive oxygen species, which themselves may cause DNA damage and are suggested to lead to carcinogenesis. To demonstrate a possible interaction between EMF and cellular systems, we present a mechanistic model describing cell activation as a major importance for cellular response.

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Effect of extremely low frequency electromagnetic fields on thromboxane B2-release by ionophore-stimulated neutrophils in vitro

Prostaglandins ◽

10.1016/0090-6980(84)90341-1 ◽

1984 ◽

Vol 27 ◽

pp. 96 ◽

Cited By ~ 1

Author(s):

P. Conti ◽

G.E. Gigante ◽

M.G. Cifone ◽

E. Alesse ◽

G. Ianni ◽

...

Keyword(s):

Electromagnetic Fields ◽

Low Frequency ◽

Thromboxane B2 ◽

Extremely Low Frequency

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Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Cav1-channel activity

Journal of Cellular Physiology ◽

10.1002/jcp.21293 ◽

2008 ◽

Vol 215 (1) ◽

pp. 129-139 ◽

Cited By ~ 136

Author(s):

Roberto Piacentini ◽

Cristian Ripoli ◽

Daniele Mezzogori ◽

Gian Battista Azzena ◽

Claudio Grassi

Keyword(s):

Electromagnetic Fields ◽

Low Frequency ◽

Channel Activity ◽

Extremely Low Frequency

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Therapeutic Application of Musically Modulated Electromagnetic Fields in the Treatment of Musculoskeletal Disorders

European Journal of Inflammation ◽

10.1177/1721727x1201000302 ◽

2012 ◽

Vol 10 (3) ◽

pp. 257-267

Author(s):

C. Corallo ◽

M. Rigato ◽

E. Battisti ◽

A. Albanese ◽

S. Gonnelli ◽

...

Keyword(s):

Electromagnetic Field ◽

Musculoskeletal Disorders ◽

Electromagnetic Fields ◽

Experimental Studies ◽

Low Frequency ◽

Experimental Point ◽

Therapeutic Application ◽

Extremely Low Frequency ◽

Positive Effects

Different studies have demonstrated the efficacy of extremely low frequency electromagnetic fields (ELF EMFs) in the treatment of pain. In particular, the positive effects of ELF EMFs seems to depend on their respective codes, such as frequency, intensity and waveform, even if the exact mechanism of interaction is still debated. The most commonly used for extremely low frequency magnetotherapy is a 100Hz sinusoidal field (ELF) with a mean of induction of few Gauss. This article reviews the therapeutic application of a musically modulated electromagnetic field (TAMMEF), a new-generation of electromagnetic field used for extremely low frequency magnetotherapy characterized by variable frequencies, intensities and waveforms. Both clinical and experimental studies, performed by authors of the present review, have demonstrated the efficacy of ELF and the new TAMMEF systems in several musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, carpal tunnel syndrome, shoulder periarthritis and cervical spondylosis. Moreover, it has been demonstrated that ELF and TAMMEF systems are not only effective, but also safe, from clinical and experimental point of view. In fact, clinical trials did not reported any undesired side effect, while in vitro studies showed that ELF EMFs did not induce uncontrolled cell proliferation, did not affect cell viability and did not induce apoptosis. With their efficacy and safety, ELF and even more the new TAMMEF systems represent a valid complementary or alternative treatment to standard pharmacological therapies in reducing both pain and inflammation of patients affected by musculoskeletal disorders.

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Extremely low frequency electromagnetic fields (ELF-EMFs) induce in vitro angiogenesis process in human endothelial cells

Bioelectromagnetics ◽

10.1002/bem.20430 ◽

2008 ◽

Vol 29 (8) ◽

pp. 640-648 ◽

Cited By ~ 39

Author(s):

Simona Delle Monache ◽

Riccardo Alessandro ◽

Roberto Iorio ◽

Giancaterino Gualtieri ◽

Rosella Colonna

Keyword(s):

Endothelial Cells ◽

Electromagnetic Fields ◽

Low Frequency ◽

Human Endothelial Cells ◽

Extremely Low Frequency ◽

Angiogenesis Process ◽

In Vitro Angiogenesis

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AHCC Activation and Selection of Human Lymphocytes via Genotypic and Phenotypic Changes to an Adherent Cell Type: A Possible Novel Mechanism of T Cell Activation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/508746 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Loretta Olamigoke ◽

Elvedina Mansoor ◽

Vivek Mann ◽

Ivory Ellis ◽

Elvis Okoro ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Immune Cell ◽

Human Lymphocytes ◽

Gene Array ◽

Adherent Cell ◽

Immune Cell Activation ◽

Wide Range

Active Hexose Correlated Compound (AHCC) is a fermented mushroom extract and immune supplement that has been used to treat a wide range of health conditions. It helps in augmentation of the natural immune response and affects immune cell activation and outcomes. The goal of this project was to study and understand the role and mechanisms of AHCC supplementation in the prevention of immunosuppression through T cell activation. The method described here involves “in vitro” culturing of lymphocytes, exposing them to different concentrations of AHCC (0 μg/mL, 50 μg/mL, 100 μg/mL, 250 μg/mL, and 500 μg/mL) at 0 hours. Interestingly, clumping and aggregation of the cells were seen between 24 and 72 hours of incubation. The cells lay down extracellular matrix, which become adherent, and phenotypical changes from small rounded lymphocytes to large macrophage-like, spindle shaped, elongated, fibroblast-like cells even beyond 360 hours were observed. These are probably translated from genotypic changes in the cells since the cells propagate for at least 3 to 6 generations (present observations). RNA isolated was subjected to gene array analysis. We hypothesize that cell adhesion is an activation and survival pathway in lymphocytes and this could be the mechanism of AHCC activation in human lymphocytes.

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