Adenosine Triphosphate Induced P2Y ₂ Receptor Activation Induces Proinflammatory Cytokine Release in Uroepithelial Cells

Abstract

Interleukin-8 and 6 release after purinergic stimulation in uroepithelial A498 cells is mediated through P2Y(2) receptor activation.

IL-8 and global gene expression analysis define a key role of ATP in renal epithelial cell responses induced by uropathogenic bacteria

“…In addition, this knockdown of P2Y2 receptor expression has previously been confirmed to not decrease other candidate receptors for ATPdependent responses in A498 cells, i.e. P2Y 11 and P2X 7 [14]. The knockdown resulted in a threefold decrease in the responsiveness to either IA2 or ATP-γ-S alone and a fourfold decrease in the responsiveness to the combination of these (Fig.…”

“…The human renal epithelial cell line A498 (HTB-44; American Tissue Culture Collection (ATCC), Manassas, VA, USA) was chosen on the basis that P2 receptor expression and ATPmediated activation of this cell line has previously been characterised [6,14], with the conclusion of the latter study that P2Y 2 receptors are responsible for ATP-mediated release of pro-inflammatory cytokines in these cells. The A498 cell line was routinely checked to be uncontaminated with respect to mycoplasma.…”

“…Recently, a non-TLR pathway has emerged that may function as a more general pathway for chemokine and cytokine release during infection. It was shown that release of IL-8 and IL-6, generally attributed to TLR4 activation during UTI, can be caused by ATP-induced P2Y 2 activation [6,14]. The recognition of this more general or alternative pathway confronts the ubiquitous role of the classical TLR4 pathway for urothelial inflammatory cell recruitment during UTI.…”

[Ca2+] Oscillations and IL-6 Release Induced by α-Hemolysin from Escherichia coli Require P2 Receptor Activation in Renal Epithelia

“…This finding strongly suggests that HlyA-induced ATP release and subsequent P2Y 2 receptor activation are required for the IL-6 secretion in ISOM. Interestingly, ATP is known to induce release of IL-6 in a P2Y 2 receptor-dependent fashion from human airway epithelia (14) and from the human renal epithelial cell line A498 (38). Because release of IL-6 is important for clearance of the bacterial infection and IL-6-deficient mice have higher mortality in response to E. coli-induced pyelonephritis (39), it would be interesting to investigate whether the same is true for P2Y 2 Ϫ/Ϫ mice.…”

Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

“…This binding and activation induces production of interleukin-8 (IL-8) by the uroepithelial cells. Binding of IL-8, plus binding of ATP to P2Y receptors on the neutrophils is required for chemotaxis of the neutrophils [32][33][34].…”