Extremely Low-Frequency: Potential Therapeutic Effects in Wound Healing

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 O2− and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E2 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, PGE2 production, catalase activity and O2− production.

Conclusions 

Mediators of inflammation, such as reactive nitrogen and PGE2, 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 PGE2, highlights the potential therapeutic role of ELF-EMF in wound healing processes.

Keywords: cyclooxygenase-2;electromagnetic field;endothelial nitric oxide synthase;inducible nitric oxide synthase;keratinocytes;wound healing

Patruno, A., Amerio, P., Pesce, M., Vianale, G., Di Luzio, S., Tulli, A., Franceschelli, S., Grilli, A., Muraro, R. and Reale, M. (2010), Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing. British Journal of Dermatology, 162: 258–266. doi: 10.1111/j.1365-2133.2009.09527.x