Stabilization of Brain Mast Cells Alleviates LPS-Induced Neuroinflammation by Inhibiting Microglia Activation

作者：Hongquan Dong, Yiming Wang, Xiaojun Zhang, Xiang Zhang, Yanning Qian, Haixia Ding, Shu Zhang · 发表于：Frontiers in Cellular Neuroscience · 年份：2019 · DOI：10.3389/fncel.2019.00191 · 被引用次数：64 · 研究领域：Mast cells and histamine、Neuroinflammation and Neurodegeneration Mechanisms、Neurological Disease Mechanisms and Treatments

Background The functional aspects of mast cell-microglia interactions are important in neuroinflammation. We have previously found that mast cell degranulation could directly induce microglia activation. However, the role of mast cell in LPS-induced microglia activation, neuroinflammation and cognitive impairment has not been clarified. Methods We studied brain microglia and mast cells interaction by site-directed injection of cromolyn in rat right hypothalamus using stereotaxic techniques. TFC and Y maze were used to assess cognitive function. Mast cells were stained by toluidine blue and calculated with Cell D software. Microglia activation was assessed by Iba1 immunohistochemistry. Conditioned medium from activated P815 cells induces microglial activation. The levels of cytokines were measured with Milliplex kit. Cell signalling was analysed by Western blotting. Results We find that “Mast cell stabilizer” cromolyn can ameliorate LPS-induced mast cells degranulation and cognitive dysfunction, and stabilization of mast cell is able to inhibit LPS-induced microglia activation, inflammatory factors release and MAPK, AKT and NF-κB signaling pathway activation in vivo and in vitro. Further LPS IP injection for 24 h induces significant microglia activation in the hypothalamus of the WT mice but has little effect on the microglia activation in KitW-sh/W-sh mice. We also find that LPS selectively provokes upregulation of expressions of H1R, H4R, PAR2, and TLR4, but deregulation of ...