The role of the JAK2-STAT3 pathway in pro-inflammatory responses of EMF-stimulated N9 microglial cells
J Neuroinflammation, (September 2010)DOI: 10.1186/1742-2094-7-54
Abstract
In several neuropathological conditions, microglia can become overactivated and cause neurotoxicity by initiating neuronal damage in response to pro-inflammatory stimuli. Our previous studies have shown that exposure to electromagnetic fields (EMF) activates cultured microglia to produce tumor necrosis factor (TNF)-α and nitric oxide (NO) through signal transduction involving the activator of transcription STAT3. Here, we investigated the role of STAT3 signaling in EMF-induced microglial activation and pro-inflammatory responses in more detail than the previous study.N9 microglial cells were treated with EMF exposure or a sham treatment, with or without pretreatment with an inhibitor (Pyridone 6, P6) of the Janus family of tyrosine kinases (JAK). The activation state of microglia was assessed via immunoreaction using the microglial marker CD11b. Levels of inducible nitric oxide synthase (iNOS), TNF-α and NO were measured using real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and the nitrate reductase method. Activation of JAKs and STAT3 proteins was evaluated by western blotting for specific tyrosine phosphorylation. The ability of STAT3 to bind to DNA was detected with an electrophoresis mobility shift assay (EMSA).EMF was found to significantly induce phosphorylation of JAK2 and STAT3, and DNA-binding ability of STAT3 in N9 microglia. In addition, EMF dramatically increased the expression of CD11b, TNF-α and iNOS, and the production of NO. P6 strongly suppressed the phosphorylation of JAK2 and STAT3 and diminished STAT3 activity in EMF-stimulated microglia. Interestingly, expression of CD11b as well as gene expression and production of TNF-α and iNOS were suppressed by P6 at 12 h, but not at 3 h, after EMF exposure.EMF exposure directly triggers initial activation of microglia and produces a significant pro-inflammatory response. Our findings confirm that the JAK2-STAT3 pathway may not mediate this initial microglial activation but does promote pro-inflammatory responses in EMF-stimulated microglial cells. Thus, the JAK2-STAT3 pathway might be a therapeutic target for reducing pro-inflammatory responses in EMF-activated microglia.
Description
I know this is terribly inconvenient news for many of us who do not have EHS. Please don’t hate the messenger, but I really think we have to be honest about this. Even if you aren’t consciously sensitive to man-made electromagnetic fields, they are bad news for anyone with chemical sensitivity (or chronic fatigue or fibromyalgia—anyone, really). The evidence for this is plain in so many studies.
Please consider taking daily, chronic EMF exposures into account. Please try to clean up the electrosmog in your living/sleeping area as much as possible. Using ethernet instead of Wifi. Keeping your phone in airplane mode as much as possible. Checking your wiring for dirty electricity. Checking for exposures coming from outside, such as nearby cell towers or a neighbor’s industrial Wifi. I hope this group can be a resource for people to do learn about how to do that to the best of our ability.
“EMF exposure directly triggers initial activation of microglia and produces a significant pro-inflammatory response.”