title: STAT3 signalling pathway is involved in the activation of microglia induced by 2.45 GHz electromagnetic fields.
abstract: OBJECTIVE
  Microglia activation plays a pivotal role in the initiation and progression of central nervous system (CNS) insult. The aim of the present work was to investigate the activation of microglia and involvement of signal transducer and activator of transcription 3 (STAT3) in microglia activation after 2.45 GHz electromagnetic fields (EMF) exposure.
  
  
  METHODS
  In this study, murine N9 microglial cells were exposed to 2.45 GHz EMF, the protein expressions of STAT3, Janus Tyrosine kinase 1 and 2(JAK1 and JAK2), phosphor-(Try705)STAT3 and DNA binding activity of STAT3 were examined by Western blot analysis and electrophoresis mobility shift assay (EMSA). Levels of the nitric oxide (NO) derivative nitrite were determined in the culture medium by the Griess reaction. The mRNA expression of tumour necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) were detected by reverse transcription and polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  A significant increase of STAT3 DNA-binding ability was noted after exposure. Consistent with this, EMF rapidly induced phosphorylation of STAT3 and activated JAK1 and JAK2. In addition, EMF exposure increased transcription levels of the inflammation-associated genes, iNOS and TNF-alpha, which are reported to contain STAT-binding elements in their promoter region. P6, a JAK inhibitor, reduced induction of iNOS and TNF-alpha, nuclear factor binding activity, and activation of STAT3 in EMF-stimulated microglia.
  
  
  CONCLUSIONS
  These results provide evidence that EMF exposure can initiate the activation of microglia cells and STAT3 signalling involves in EMF-induced microglial activation.
authors.affiliation: Key laboratory of Medical Protection for Electromagnetic radiation Ministry of Education, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Hao
authors.forename: Xuesen
authors.initials: X
authors.lastname: Yang
authors.forename: Chunhai
authors.initials: C
authors.lastname: Chen
authors.lastname: Yuan-Wang
authors.forename: Xubu
authors.initials: X
authors.lastname: Wang
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004574:Electromagnetic Fields; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000528:radiation effects*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation; D011728:Pyridones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C524063:2-tert-butyl-9-fluoro-3,6-dihydro-7H-benz(h)imidazo(4,5-f)isoquinoline-7-one; D001562:Benzimidazoles; D011728:Pyridones; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D052247:Nitric Oxide Synthase Type II; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2