Role of mast cell activation in inducing microglial cells to release neurotrophin.
The brain-derived neurotrophic factor (BDNF) plays a critical role in pain hypersensitivity. BDNF is the ligand of P2X4 receptors (P2X4R) in the microglia. The causative factors involving the P2X4R over expression in the microglia remains unclear. Mast cell activation has a close relation with pain hypersensitivity. However, the underlying mechanism between mast cell activation and pain hypersensitivity is unknown. The present study aimed to elucidate the mechanism by which mast cell activation promoted the expression of P2X4R in the microglia. The results of present study showed that mast cell activation markedly promoted the expression of P2X4R and BDNF in microglial cells, which significantly enhanced the release of BDNF from microglial cells upon exposure to adenosine triphosphate. Mast cell-derived tryptase activated PAR2 that resulted in promoting the expression of P2X4R in microglial cells. Pretreatment with antibodies against tryptase or PAR2, or using tryptase-deficient HMC-1 cells or PAR2-deficient microglial cells abolished the increase in P2X4R expression and BDNF release. Increase in mitogen activated protein kinase phosphorylation was observed in the processes of mast cell-induced BDNF release and P2X4R expression. We conclude that mast cell activation has the capacity to promote the expression of P2X4R and BDNF in microglial cells.
Yuan
Hongbin
H
Department of Anesthesiology, Changzheng Hospital, the Second Military Medical University, Shanghai, China.
Zhu
Xiaoling
X
Zhou
Shuangqiong
S
Chen
Qianbo
Q
Zhu
Xiaoxing
X
Ma
Xue
X
He
Xingying
X
Tian
Mouli
M
Shi
Xueyin
X
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D010766:Phosphorylation; D044464:Receptor, PAR-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4; D053802:Tryptases / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C548226:P2RX4 protein, human; C548227:P2rx4 protein, mouse; D044464:Receptor, PAR-2; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D048049:Extracellular Signal-Regulated MAP Kinases; D053802:Tryptases; D000251:Adenosine Triphosphatases