Cells were incubated with or without LPS (as positive control for cell activation).
Under physiological conditions, the proteolytic activity of matrix metalloproteinases (MMPs) is regulated by the tissue inhibitors of metalloproteinases (TIMPs). An undisrupted balance between MMPs and TIMPs is necessary for the maintenance of normal cellular function.
|Setup||22 cm long solenoid with a radius of 6 cm and 160 turns of 1.25 x 10-5 cm diameter copper wire; solenoid placed inside an incubator with a constant temperature of 37°C and 5% CO2 atmosphere; cell cultures located at the center region of the solenoid; field homogeneity in the exposure area = 98%|
|Sham exposure||A sham exposure was conducted.|
The electromagnetic field (EMF) exposure induced a weak increase of spontaneous matrix metalloproteinase-9 (MMP-9) mRNA expression, while higher induction was observed for matrix metalloproteinase-2 (MMP-2) mRNA expression. The LPS-induced MMP-9 mRNA expression was potentiated by EMF-exposure, while a moderate effect was found for MMP-2.
In the EMF exposed cells, the lytic enzyme activity of MMP-9 was more intense corresponding with a higher MMP-9 mRNA level. The combination of LPS and EMF exposure increased MMP-9 enzyme activity compared to cells treated with LPS alone. However, MMP-2 enzyme activity was not modified by LPS stimulation nor/or EMF-exposure.
iNOS enzyme activity, mRNA expression and protein expression were increased in exposed cells compared with controls. Co-exposure of electromagnetic fields and LPS resulted in a reduced mRNA expression of iNOS and a less effective induction of the protein expression compared with cells treated with LPS alone.
Cells exposed to EMF caused a reduction of antioxidant enzyme activities (superoxide dismutase and catalase) and an enhancement of nitrogen intermediates (cGMP) involving the iNOS pathway.
The EMF exposure markedly reduced TIMP-1 enzyme activity when compared with control cells. Molecular modeling was employed to identify the most plausible nitration sites in the active conformation of TIMP-1.
These results may suggest a pathway connecting an imbalance of MMPs and their inhibitor TIMP-1. The authors conclude that the relationship between elements of oxidative stress/nitrosative stress and MMPs activation is modulated by EMF exposure. This effect may play a significant role in many disease processes.