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Background:
Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes.
Objectives:
The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing.
Methods:
Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O(2)(-) and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E(2) production were determined. Effects of ELF-EMF on cell growth and viability were monitored.
Results:
The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE(2) production, catalase activity and O(2)(-) production.
Conclusions:
Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.
The effect of extremely low frequency (ELF) electromagnetic field (EMF) (50 Hz 0.5 mT) on the activity of acid phosphatase (EC 3.1.3.2) was studied. In addition the factors affecting the enzyme activity such as the temperature, pH and substrate concentration were also investigated. The results show that ELF EMF have significant influence on enzyme activity. Upon EMF exposure Km increased from 0014 ± 0.005 to 0.040 ± 0.008 mM whereas Vmax increased from 0.991 ± 0.254 to 1.638 ± 0.345 µmol/min. Further studies can probably help in finding suitable applications for ELF based modulation of enzyme activity.
Activated microglia surrounding amyloid β-containing senile plaques synthesize interleukin-1, an inflammatory cytokine that has been postulated to contribute to Alzheimer's disease pathology. Studies have demonstrated that amyloid β treatment causes increased cytokine release in microglia and related cell cultures. The present work evaluates the specificity of this cellular response by comparing the effects of amyloid β to that of amylin, another amyloidotic peptide. Both lipopolysaccharide-treated THP-1 monocytes and mouse microglia showed significant increases in mature interleukin-1β release 48 h following amyloid β or human amylin treatment, whereas nonfibrillar rat amylin had no effect on interleukin-1β production by THP-1 cells. Lipopolysacharide-stimulated THP-1 cells treated with amyloid β or amylin also showed increased release of the proinflamatory cytokines tumor necrosis factor-α and interleukin-6, as well as the chemokines interleukin-8 and macrophage inflammatory protein-1 α and -1β. THP-1 cells incubated with fibrillar amyloid β or amylin in the absence of lipopolysaccharide also showed significant increases of both interleukin-1β and tumor necrosis factor-α mRNA. Furthermore, treatment of THP-1 cells with amyloid fibrils resulted in an elevated expression of the immediate-early genes c-fos and junB. These studies provide further evidence that fibrillar amyloid peptides can induce signal transduction pathways that initiate an inflammatory response that is likely to contribute to Alzheimer's disease pathology.
Oxidative stress is associated with a number of degenerative disease states, such as cancer and AIDS. Fundamental to oxidative stress is the generation of superoxide, peroxide and other reactive oxygen species (ROS). This review focuses on the importance of cytochrome P450 (CYP) enzymes in the activation of oxygen and ROS generation, together with a discussion of defence mechanisms which can offer protection against oxidative stress.
© 2002 Society of Chemical Industry.
Microglia are associated with central nervous system (CNS) pathology of both Alzheimer's disease (AD) and the acquired immunodeficiency syndrome (AIDS). In AD, microglia, especially those associated with amyloid deposits, have a phenotype that is consistent with a state of activation, including immunoreactivity with antibodies to class II major histocompatibility antigens and to inflammatory cytokines (interleukin-1-β and tumor necrosis factor-α). Evidence from other studies in rodents indicate that microglia can be activated by neuronal degeneration. These results suggest that microglial activation in AD may be secondary to neurodegeneration and that, once activated, microglia may participate in a local inflammatory cascade that promotes tissue damage and contributes to amyloid formation. In AIDS, microglia are the primary target of retroviral infection. Both ramified and ameboid microglia, in addition to multinucleated giant cells, are infected by the human immunodeficiency virus (HIV-1). The mechanism of microglial infection is not known since microglia lack CD4, the HIV-1 receptor. Microglia display high affinity receptors for immunoglobulins, which makes antibody-mediated viral uptake a possible mechanism of infection. In AIDS, the extent of active viral infection and cytokine production may be critically dependent upon other factors, such as the presence of coinfecting agents. In the latter circumstance, very severe CNS pathology may emerge, including necrotizing lesions. In other circumstances, HIV infection microglia probably leads to CNS pathology by indirect mechanisms, including release of viral proteins (gp120) and toxic cytokines. Such a mechanism is the best hypothesis for the pathogenesis of vacuolar myelopathy in adults and the diffuse gliosis that characterizes pediatric AIDS, in which very little viral antigen can be detected.
In attempt to meet tissue demands for proper blood flow, the vasculature alters its structure, simultaneously responding to both physical and chemical stresses. Substantial information has emerged in this field of study, particularly concerning the roles of the endothelium and smooth muscle cells in relation to signaling pathways for mechanotransduction. As a first line of defense upon exposure to various stressors, the endothelium and smooth muscle cells respond with adaptive cellular modifications. One prime example of these modifications is the cellular response to oxidative stress as evidenced by accumulated data. A recent proposal of the inflammatory hypothesis of vascular aging emphasized that stress-induced vascular aging may be the primary event that underlies the general aging phenomenon of systemic dysfunction.
Recently, a number of epidemiological studies have suggested that occupational as well as residential exposure to extreme low-frequency electromagnetic fields (ELF-EMFs) may be a risk factor for Alzheimer's disease. This is not proven yet and there are no known biological mechanisms to explain this alleged association. Alzheimer's disease is characterized by a number of events that have, at least partially, a genetic origin. In particular, trisomy of chromosomes 17 and 21 seems to be involved. Overall ELF-EMFs have not been identified as genotoxic agents, but there are some papers in the scientific literature that indicate that they may enhance the effects of agents that are known to induce mutations or tumors. There are also some indications that ELF-EMFs may induce aneuploïdy. This opens some perspectives for investigating the alleged association between ELF-EMFs and Alzheimer's. This paper reviews the possibility of a cytogenetic association between the electromagnetic fields and Alzheimer's disease.