To study, in more detail than in a previous study (Hao et al. 2010), the activation of microglia and involvement of signal transducer and activator of transcription 3 (STAT3; mediates signal transduction from the extracellular environment to the nucleus) in microglia activation after 2.45 GHz electromagnetic fields exposure.
Microglia is considered as a specialised macrophages residing form in the central nervous system. In response to a variety of insults, microglia adopts an activated phenotype. Microglia activation plays a pivotal role in the initiation and progression of several neurodegenerative diseases.
Some cell samples were pretreated with the JAK inhibitor pyridone 6 (P6) to study whether P6 could affect the STAT3 activation (to further demonstrate JAK2-STAT3 signal transduction (JAK is a STAT3 activator and is able to phosphorylate STAT3)). Cells were investigated 1 h, 3 h, 6 h, 12 h, and 24 h after exposure.
A part of the cells were pretreated with Pyridone 6
| Frequency | 2.45 GHz |
|---|---|
| Type | |
| Exposure duration | continuous for 20 min |
| Modulation type | pulsed |
|---|---|
| Pulse width | 2 µs |
| Packets per second | 500 |
| Exposure source |
|
|---|---|
| Distance between exposed object and exposure source | 90 cm |
| Chamber | anechoic chamber with a temperature of 25° C - 26° C |
| Setup | four flasks placed in a 24.5 cm x 21 cm water bath at 37° C; irradiation directed downward from the rectangular horn antenna to the flasks by a refector |
| Sham exposure | A sham exposure was conducted. |
The data showed that the electromagnetic field exposure significantly induced the phosphorylation of JAK2 and STAT3 (time-dependent manner with peak at 12 h), and the DNA-binding ability of STAT3 in N9 microglia. Additionally, electromagnetic field exposure dramatically increased the expression of CD11b, tumor necrosis factor-alpha and inducible nitric oxide synthase (iNOS), and the production of nitric oxide.
P6 strongly suppressed the phosphorylation of JAK2 and STAT3 and decreased the STAT3 activity in electromagnetic field-stimulated microglia. Interestingly, expression of CD11b as well as gene expression and production of tumor necrosis factor-alpha and inducible nitric oxide synthase (iNOS) were suppressed by P6 at 12 h, but not at 3 h after electromagnetic field exposure.
In conclusion, the electromagnetic field exposure directly triggered an initial activation of microglia and produced a significant pro-inflammatory response. Activation of JAK2-STAT3 signaling occured in parallel with the microglial activation and the release of pro-inflammatory factors (i.e. tumor necrosis factor-alpha, iNOS and nitric oxide). Microglia activation and pro-inflammatory responses were significantly reduced by P6 at 12 h, but not at 3 h after electromagnetic field exposure. These data suggest that the JAK2-STAT3 pathway may not mediate the initial microglial activation but does promote pro-inflammatory responses in electromagnetic field-stimulated microglial cells. The data provide a basis to determine whether the pro-inflammatory responses of electromagnetic field-stimulated microglia can be suppressed by inhibition of the JAK2-STAT3 pathway in therapeutic interventions.
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