Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X(4) in rat urothelial cells.
Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X(4) in rat urothelial cells.
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DOI：
10.1007/s11255-018-1948-0
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发表时间：
2018-09
影响因子：
2
通讯作者：
Nagatomi J
中科院分区：
文献类型：
--
作者：
Dunton CL;Purves JT;Hughes FM Jr;Jin H;Nagatomi J
部分膀胱出口梗阻（pBOO）是一种常见的泌尿系统疾病，通常伴有膀胱内压升高、炎症和纤维化。研究表明，pBOO导致NLRP 3炎性体和半胱天冬酶-1活化增加，并且ATP响应于升高的压力从尿路上皮细胞释放。在本研究中，我们研究了压力升高在通过嘌呤能受体激活尿路上皮细胞中触发半胱天冬酶-1激活中的作用。使大鼠尿路上皮细胞系MYP 3细胞经受15 cmH 2 O的流体静压60分钟或40 cmH 2 O的流体静压1分钟以分别模拟升高的储存和排泄压力条件。测量上清液培养基中的ATP浓度和细胞裂解物中的细胞内半胱天冬酶-1活性。在嘌呤受体拮抗剂存在下重复压力实验，以确定压力诱导的caspase-1活化的机制。MYP 3细胞暴露于两种压力条件下导致细胞外ATP水平和细胞内caspase-1活性增加。P2 X7拮抗剂处理导致压力诱导的MYP 3细胞ATP释放减少，而P2 X4拮抗剂没有影响，但两种拮抗剂都抑制压力诱导的caspase-1活化。此外，当用细胞外ATP（500 μM）处理MYP 3细胞时，P2 X4拮抗剂抑制ATP诱导的caspase-1活化，而P2 X7拮抗剂则不抑制。我们的结论是，压力诱导的细胞外ATP在尿路上皮细胞的放大P2 X7受体激活和ATP诱导的ATP释放。放大的ATP信号然后激活P2 X4受体，其介导半胱天冬酶-1炎症反应的激活。
Partial bladder outlet obstruction (pBOO) is a prevalent urological condition commonly accompanied by increased intravesical pressure, inflammation and fibrosis. Studies have demonstrated that pBOO results in increased NLRP3 inflammasome and caspase-1 activation and that ATP is released from urothelial cells in response to elevated pressure. In the present study, we investigated the role of elevated pressure in triggering caspsase-1 activation via purinergic receptors activation in urothelial cells. Rat urothelial cell line, MYP3 cells, were subjected to hydrostatic pressures of 15 cmH2O for 60 minutes, or 40 cmH2O for 1 minute to simulate elevated storage and voiding pressure conditions, respectively. ATP concentration in the supernatant media and intracellular caspase-1 activity in cell lysates were measured. Pressure experiments were repeated in the presence of antagonists for purinergic receptors to determine the mechanism for pressure-induced caspase-1 activation. Exposure of MYP3 cells to both pressure conditions resulted in an increase in extracellular ATP levels and intracellular caspase-1 activity. Treatment with P2X7 antagonist led to a decrease in pressure-induced ATP release by MYP3 cells, while P2X4 antagonist had no effect but both antagonists inhibited pressure induced caspase-1 activation. Moreover, when MYP3 cells were treated with extracellular ATP (500 µM), P2X4 antagonist inhibited ATP-induced caspase-1 activation, but not P2X7 antagonist. We concluded that pressure-induced extracellular ATP in urothelial cells is amplified by P2X7 receptor activation and ATP-induced-ATP release. The amplified ATP signal then activates P2X4 receptors, which mediate activation of the caspase-1 inflammatory response.
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影响因子：
3.8
作者：
Hazama, A;Shimizu, T;Okada, Y
通讯作者：
Okada, Y
DOI：
10.1152/ajprenal.00297.2013
发表时间：
2014-02-01
影响因子：
4.2
作者：
Hughes, Francis M., Jr.;Vivar, Nivardo P.;Purves, J. Todd
通讯作者：
Purves, J. Todd
影响因子：
8
作者：
Glass, R;Loesch, A;Burnstock, G
通讯作者：
Burnstock, G
影响因子：
5.4
作者：
Hornung, Veit;Latz, Eicke
通讯作者：
Latz, Eicke
DOI：
10.1016/j.juro.2015.12.068
发表时间：
2016-05
期刊：
The Journal of urology
影响因子：
--
作者：
Hughes FM Jr;Hill HM;Wood CM;Edmondson AT;Dumas A;Foo WC;Oelsen JM;Rac G;Purves JT
通讯作者：
Purves JT