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Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells.

Publication ,  Journal Article
Dunton, CL; Purves, JT; Hughes, FM; Jin, H; Nagatomi, J
Published in: Int Urol Nephrol
September 2018

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.

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Published In

Int Urol Nephrol

DOI

EISSN

1573-2584

Publication Date

September 2018

Volume

50

Issue

9

Start / End Page

1607 / 1617

Location

Netherlands

Related Subject Headings

  • Urothelium
  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Purinergic P2X4
  • Rats
  • Purinergic P2X Receptor Antagonists
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • Hydrostatic Pressure
  • Female
 

Citation

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Dunton, C. L., Purves, J. T., Hughes, F. M., Jin, H., & Nagatomi, J. (2018). Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells. Int Urol Nephrol, 50(9), 1607–1617. https://doi.org/10.1007/s11255-018-1948-0
Dunton, Cody L., J Todd Purves, Francis M. Hughes, Huixia Jin, and Jiro Nagatomi. “Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells.Int Urol Nephrol 50, no. 9 (September 2018): 1607–17. https://doi.org/10.1007/s11255-018-1948-0.
Dunton CL, Purves JT, Hughes FM, Jin H, Nagatomi J. Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells. Int Urol Nephrol. 2018 Sep;50(9):1607–17.
Dunton, Cody L., et al. “Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells.Int Urol Nephrol, vol. 50, no. 9, Sept. 2018, pp. 1607–17. Pubmed, doi:10.1007/s11255-018-1948-0.
Dunton CL, Purves JT, Hughes FM, Jin H, Nagatomi J. Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells. Int Urol Nephrol. 2018 Sep;50(9):1607–1617.
Journal cover image

Published In

Int Urol Nephrol

DOI

EISSN

1573-2584

Publication Date

September 2018

Volume

50

Issue

9

Start / End Page

1607 / 1617

Location

Netherlands

Related Subject Headings

  • Urothelium
  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Purinergic P2X4
  • Rats
  • Purinergic P2X Receptor Antagonists
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • Hydrostatic Pressure
  • Female