title: The role of the NF-κB, SAPK/JNK, and TLR4 signalling pathways in the responses of RAW 264.7 cells to extremely low-intensity microwaves.
abstract: OBJECTIVE
  To investigate the role of the toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), and stress activated protein kinases/Jun N-terminal kinase (SAPK/JNK) signalling pathways in the responses of RAW 264.7 macrophages to low-intensity microwaves (MW).
  
  
  METHODS
  Three inhibitors of TLR4, SAPK/JNK, and NF-κB signalling, namely CLI-095, SP600125, and IKK Inhibitor XII, respectively, were added to cultured RAW 264.7 macrophages before MW treatment.
  
  
  RESULTS
  MW exposure resulted in stimulation of RAW 264.7 cell activity manifested by increases in cytokine production and the stimulation of cell signalling. The blocking of a key kinase of the NF-κB pathway by IKK Inhibitor XII resulted in decreased MW-induced TLR4 expression and increased SAPK/JNK and NF-κB phosphorylation in irradiated cells. In addition, IKK Inhibitor XII significantly decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 1α (IL-1α), interleukin 6 (IL-6), and interleukin 10 (IL-10) production in both exposed and unexposed RAW 264.7 macrophages. Inhibitor SP6000125 did not prevent an MW effect on signal proteins with the exception of decreased SAPK/JNK phosphorylation in RAW 264.7 cells. Cytokine production was markedly decreased in MW-exposed cells cultured with SP6000125. The inhibitor of TLR4, CLI-095, did not affect signal proteins and cytokine production changes in MW-exposed cells.
  
  
  CONCLUSIONS
  The results suggest that low-intensity MW promotes macrophage activity via mechanisms involving cellular signalling, particularly the NF-κB pathway.
authors.affiliation: Institute of Cell Biophysics RAS , Pushchino , Russian Federation.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Glushkova
authors.forename: Maxim O
authors.initials: MO
authors.lastname: Khrenov
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Novoselova
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Lunin
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Parfenyuk
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Alekseev
authors.forename: Eugeny E
authors.initials: EE
authors.lastname: Fesenko
authors.forename: Elena G
authors.initials: EG
authors.lastname: Novoselova
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008264:Macrophages / Q000528:radiation effects*; D051379:Mice; D008872:Microwaves / Q000009:adverse effects*; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048031:JNK Mitogen-Activated Protein Kinases
keywords: NF-κB; RAW 264.7 cells; SAPK/JNK; TLR4; microwaves