NFAT公司
脱颗粒
炎症
细胞因子
细胞生物学
生物
免疫学
免疫系统
嗜酸性粒细胞
启动(农业)
肥大细胞
刺激
白细胞介素33
钙调神经磷酸酶
受体
白细胞介素
转录因子
医学
生物化学
神经科学
内科学
基因
发芽
哮喘
植物
移植
作者
David B. Straus,Destiny T. Pryor,Tamara T. Haque,Sydney Ann Kee,Jordan Dailey,Kasey L. Jackson,Brian Barnstein,John Ryan
标识
DOI:10.1016/j.cellimm.2021.104470
摘要
Inflammatory responses are required to block pathogen infection but can also lead to hypersensitivity and chronic inflammation. Barrier tissues actively release IL-33, ATP, and other alarmins during cell stress, helping identify pathogenic stimuli. However, it is unclear how these signals are integrated. Mast cells are critical initiators of allergic inflammation and respond to IL-33 and ATP. We found that mouse mast cells had a 3-6-fold increase in ATP-induced cytokine production when pre-treated with IL-33. This effect was observed at ATP concentrations < 100 µM and required < 30-minute IL-33 exposure. ATP-induced degranulation was not enhanced by pretreatment nor was the response to several pathogen molecules. Mechanistic studies implicated the P2X7 receptor and calcineurin/NFAT pathway in the enhanced ATP response. Finally, we found that IL-33 + ATP co-stimulation enhanced peritoneal eosinophil and macrophage recruitment. These results support the hypothesis that alarmins collaborate to surpass a threshold necessary to initiate an inflammatory response.
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