Hu Bing, Feng Xiaoqian, Wang Li, Song Yinli, Ni Xiuqin
Department of Anatomy, Harbin Medical University Daqing, Daqing, 163319, Heilongjiang Province, China.
Department of Pathology, Harbin Medical University Daqing, Daqing 163319, Heilongjiang Province, China.
Iran J Basic Med Sci. 2018 Apr;21(4):364-369. doi: 10.22038/IJBMS.2018.25731.6345.
P2X4R is expressed in immunocyte and lung tissues. It has been a focus in inflammatory responses recently. This study investigated whether blockage of P2X4R attenuates allergic inflammation by modulating T cell response in ovalbumin-sensitized mice.
Ovalbumin was used to sensitize and challenge for a mouse model. Intranasal application of 5-BDBD, P2X4R antagonist, were performed 3 hr before each airway allergen challenge. The lung was evaluated for P2X4R by real-time PCR and immunofluorescence. Th1/Th2 cytokines in bronchoalveolar lavage fluid were measured by ELISA. T-bet, Gata-3, and p-p38 MAPK were measured by Western blot or real-time PCR.
P2X4R was overexpressed in the lung after allergen challenge compared with the control group. Blockage of P2X4R decreased inflammation in the lung, IL-4 expression was reduced as well as IL-5; IFN-γ expression was elevated in BALF in ovalbumin-sensitized mice. Moreover, blockage of P2X4R inhibited ovalbumin-induced increased Gata-3 level and decreased T-bet level.
These findings suggest that 5-BDBD ameliorates an ovalbumin-induced asthmatic attack by the downregulation of cytokines related to the Th2 cell.
P2X4R在免疫细胞和肺组织中表达。它最近一直是炎症反应的研究热点。本研究调查了阻断P2X4R是否通过调节卵清蛋白致敏小鼠的T细胞反应来减轻过敏性炎症。
用卵清蛋白对小鼠模型进行致敏和激发。在每次气道过敏原激发前3小时经鼻给予P2X4R拮抗剂5-BDBD。通过实时PCR和免疫荧光评估肺组织中的P2X4R。用ELISA检测支气管肺泡灌洗液中的Th1/Th2细胞因子。通过蛋白质免疫印迹法或实时PCR检测T-bet、Gata-3和p-p38 MAPK。
与对照组相比,过敏原激发后肺组织中P2X4R过表达。阻断P2X4R可减轻肺部炎症,IL-4和IL-5的表达降低;卵清蛋白致敏小鼠的BALF中IFN-γ表达升高。此外,阻断P2X4R可抑制卵清蛋白诱导的Gata-3水平升高和T-bet水平降低。
这些发现表明,5-BDBD通过下调与Th2细胞相关的细胞因子来改善卵清蛋白诱导的哮喘发作。