文章基本信息

标题：Extracellular ATP mediates inflammatory responses in colitis via P2 × 7 receptor signaling
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作者：Ping Wan ; Xiaopeng Liu ; Yan Xiong 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
DOI：10.1038/srep19108
出版社：Springer Nature
摘要：Extracellular purinergic products, particularly ATP, have recently been implicated to regulate immune cell functions and contribute to aberrant inflammatory responses of immune diseases. However, regulation of immune responses of colitis by extracellular ATP and its main receptor, P2 × 7, remains to be elucidated. In the study, we induced murine colitis by feeding mice with 4% dextran sulfate sodium (DSS), and noted dramatically heightened extracellular ATP levels in colon tissues during the progression of experimental colitis. Blockade of ATP release by carbenoxolone (CBX) treatment, or promoting ATP degradation by ATP diphosphohydrolase (apyrase), decreased extracellular ATP levels in colon tissues, attenuated DSS-induced colitis, whereas inhibition of extracellular ATP degradation by sodium metatungstate (POM-1) exacerbated tissue damage in the mice with colitis. Moreover, treatment with inhibitor of P2 × 7 receptor, A438079, decreased NFκB activation and active caspase-1 expression in lamina propria immune cells, downregulated proinflammatory cytokine production in colon tissues, and attenuated murine colitis. Collectively, these data suggest extracellular ATP participates in regulation of inflammatory responses of experimental colitis, through P2 × 7 receptor and inflammasome and NFκB signaling, which provides potential alternatives to the current clinical approaches to suppress extracellular ATP-mediated immune responsiveness.