Induction of Microglial Activation by Mediators Released from Mast Cells

Background/Aims: Microglia are the resident immune cells in the brain and playa 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 ELEA 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 INF-alpha and IL-6. Co-culture of microglia and HMC-1 cells with corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased INF-alpha and IL-6 production. Antagonists of histamine receptor 1 (HiR), 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. (C) 2016 The Author(s) Published by S. Karger AG, Basel