title: Induction of Microglial Activation by Mediators Released from Mast Cells.
abstract: OBJECTIVE
  Microglia are the resident immune cells in the brain and play a pivotal role in immune surveillance in the central nervous system (CNS). Brain mast cells are activated in CNS disorders and induce the release of several mediators. Thus, brain mast cells, rather than microglia, are the "first responders" due to injury. However, the functional aspects of mast cell-microglia interactions remain uninvestigated.
  
  
  METHODS
  Conditioned medium from activated HMC-1 cells induces microglial activation similar to co-culture of microglia with HMC-1 cells. Primary cultured microglia were examined by flow cytometry analysis and confocal microscopy. TNF- alpha and IL-6 were measured with commercial ELISA kits. Cell signalling was analysed by Western blotting.
  
  
  RESULTS
  In the present study, we found that the conditioned medium from activated HMC-1 cells stimulated microglial activation and the subsequent production of the pro-inflammatory factors TNF-α and IL-6. Co-culture of microglia and HMC-1 cells with corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased TNF-α and IL-6 production. Antagonists of histamine receptor 1 (H1R), H4R, proteinase-activated receptor 2 (PAR2) or Toll-like receptor 4 (TLR4) reduced HMC-1-induced pro-inflammatory factor production and MAPK and PI3K/AKT pathway activation.
  
  
  CONCLUSIONS
  These results imply that activated mast cells trigger microglial activation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS inflammation-related diseases.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Dong
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D017077:Culture Media, Conditioned; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D015850:Interleukin-6; D044464:Receptor, PAR-2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D003346:Corticotropin-Releasing Hormone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases