Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation

Molecular Neurobiology
Hongquan DongShu Zhang

Abstract

Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H1R), histamine receptor 4 (H4R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient KitW-sh/W-sh mice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial a...Continue Reading

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Citations

Apr 18, 2016·Clinical Therapeutics·Zuyi WengTheoharis C Theoharides
Nov 11, 2017·Journal of Integrative Neuroscience·Giovanna Traina
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Aug 3, 2021·Frontiers in Neuroscience·Elliott Carthy, Tommas Ellender
Nov 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan P MendozaJared M Brown

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Methods Mentioned

BETA
ELISA
electrophoresis
flow cytometry

Software Mentioned

CellQuest
Cell D

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