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• W2887772306 abstract "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 caspase-1 activation via purinergic receptors activation in urothelial cells. Rat urothelial cell line, MYP3 cells, was subjected to hydrostatic pressures of 15 cmH2O for 60 min, or 40 cmH2O for 1 min 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." @default.
• W2887772306 created "2018-08-22" @default.
• W2887772306 creator A5001824703 @default.
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• W2887772306 date "2018-08-11" @default.
• W2887772306 modified "2023-10-16" @default.
• W2887772306 title "Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells" @default.
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• W2887772306 doi "https://doi.org/10.1007/s11255-018-1948-0" @default.
• W2887772306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6129973" @default.
• W2887772306 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30099658" @default.
• W2887772306 hasPublicationYear "2018" @default.
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