小胶质细胞
嗅球
受体
发病机制
嗅觉系统
化学
卵清蛋白
敏化
效应器
免疫学
细胞生物学
生物
内分泌学
免疫系统
神经科学
炎症
生物化学
中枢神经系统
作者
Chao Ren,Yakui Mou,Xiao‐Yu Song,Shi‐Zhuang Wei,Hanrui Wang,Yao Wang,Wen‐Bin Zhang,Bing Li,Xicheng Song
标识
DOI:10.1096/fj.202300160rr
摘要
Abstract The pathogenesis of allergic rhinitis (AR)‐related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR‐related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)‐induced AR and combined with the application of P2X7 receptor (P2X7R)‐specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR‐related OD. Serum IgE and IL‐5 levels determined via ELISA and federated the number of nose‐scratching to affirm the success of OVA‐induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL‐1β, IL‐1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR‐related OD was associated with OB microglia‐mediated imbalance between IL‐1β and IL‐1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL‐1β and IL‐1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on “ATP‐P2X7R‐Caspase 1” axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR‐related OD and inhibition of it may be a new strategy for the treatment of AR‐related OD.
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