P2Y6 contributes to ovalbumin-induced allergic asthma by enhancing mast cell function in mice.
P2Y6 contributes to ovalbumin-induced allergic asthma by enhancing mast cell function in mice.
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DOI：
10.18632/oncotarget.11758
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Ren H
中科院分区：
文献类型：
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作者：
Shi JP;Wang SY;Chen LL;Zhang XY;Zhao YH;Du B;Jiang WZ;Qian M;Ren H
细胞外核苷酸通过激活嘌呤能受体被认为是哮喘发病的调节因子。本研究旨在探讨嘌呤能受体P2Y6在过敏性哮喘气道炎症中的作用。用卵清蛋白(OVA)刺激野生型(WT)和P2Y6基因缺陷小鼠建立哮喘小鼠模型。卵白蛋白诱导的哮喘小鼠肺组织中存在高表达的P2Y6和尿苷二磷酸(UDP)释放。哮喘小鼠应用UDP后，细胞因子IL-4的释放、肥大细胞的侵袭和气道重塑表型加重。然而，在小鼠模型中，P2Y6缺乏显著减少了这些哮喘的致病症状。在体外，我们发现纯化的肥大细胞中的P2Y6通过触发肥大细胞的迁移、细胞因子分泌和颗粒释放来增强肥大细胞在哮喘过程中的炎症反应功能。此外，P2Y6通过激活AKT信号通路来刺激肥大细胞的功能。我们的数据提供了证据，在卵白蛋白诱导的哮喘小鼠中，P2Y6通过增强肥大细胞的功能而促进过敏性气道炎症和重塑。
Extracelluar nucleotides have been identified as regulatory factors in asthmatic pathogenesis by activating purinergic receptors. This research aimed to investigate the function of the purinergic receptor P2Y6 in mediating airway inflammation in allergic asthma. Wild-type (WT) and P2Y6-deficient mice were stimulated with ovalbumin (OVA) to construct asthmatic mouse models. Overexpression of P2Y6 and uridine 5′-diphosphate (UDP)-releasing were demonstrated in lung tissues in ovalbumin-induced asthmatic mice. The release of the cytokine IL-4, mast cell invasion, and the airway remodeling phenotypes were more severe following the application of UDP in asthmatic mice. However, P2Y6 deficiency reduced these asthmatic pathogeneticsymptoms markedly in a mouse model. In vitro, we found that P2Y6 in purified mast cells enhanced the functions of mast cells in the inflammatory response in the asthmatic process by triggering their capability for migration, cytokine secretion and granule release. Moreover, P2Y6 stimulated the function of mast cells through activation of the AKT signaling pathway. Our data provides evidence that P2Y6 contributes to allergic airway inflammation and remodeling by enhancing the functions of mast cells in ovalbumin-induced asthmatic mice.