[Ca2+]i Oscillations and IL-6 Release Induced by α-Hemolysin from Escherichia coli Require P2 Receptor Activation in Renal Epithelia
| Autor: | Steen K. Fagerberg, Mette G. Christensen, Jens Leipziger, Randi G. Bjaelde, Pauline I.A. de Bruijn, Helle Jakobsen, Marianne Skals, Helle A. Praetorius |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
P2 receptor Biology urologic and male genital diseases Kidney Biochemistry Cell Line Receptors Purinergic P2Y2 chemistry.chemical_compound Hemolysin Proteins Mice fluids and secretions Adenosine Triphosphate Dogs Internal medicine medicine Extracellular Escherichia coli Animals Humans Calcium Signaling Receptor Molecular Biology Escherichia coli Infections Calcium signaling Interleukin-6 Escherichia coli Proteins Cell Biology Purinergic signalling biochemical phenomena metabolism and nutrition bacterial infections and mycoses Cell biology medicine.anatomical_structure Endocrinology chemistry Renal physiology bacteria Urothelium Adenosine triphosphate |
| Zdroj: | Christensen, M, Fagerberg, S K, de Bruijn, P I A, Bjælde, R G, Jakobsen, H, Leipziger, J G, Skals, M G & Prætorius, H 2015, ' [Ca2+]i oscillations and IL-6 release induced by alpha-hemolysin from Escherichia coli require P2 receptor activation in renal epithelia ', Journal of Biological Chemistry, vol. 290, no. 23, pp. 14776-84 . https://doi.org/10.1074/jbc.M115.639526 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M115.639526 |
| Popis: | Urinary tract infections are commonly caused by α-hemolysin (HlyA)-producing Escherichia coli. In erythrocytes, the cytotoxic effect of HlyA is strongly amplified by P2X receptors, which are activated by extracellular ATP released from the cytosol of the erythrocytes. In renal epithelia, HlyA causes reversible [Ca2+]i oscillations, which trigger interleukin-6 (IL-6) and IL-8 release. We speculate that this effect is caused by HlyA-induced ATP release from the epithelial cells and successive P2 receptor activation. Here, we demonstrate that HlyA-induced [Ca2+]i oscillations in renal epithelia were completely prevented by scavenging extracellular ATP. In accordance, HlyA was unable to inflict any [Ca2+]i oscillations in 132-1N1 cells, which lack P2R completely. After transfecting these cells with the hP2Y2 receptor, HlyA readily triggered [Ca2+]i oscillations, which were abolished by P2 receptor antagonists. Moreover, HlyA-induced [Ca2+]i oscillations were markedly reduced in medullary thick ascending limbs isolated from P2Y2 receptor-deficient mice compared with wild type. Interestingly, the following HlyA-induced IL-6 release was absent in P2Y2 receptor-deficient mice. This suggests that HlyA induces ATP release from renal epithelia, which via P2Y2 receptors is the main mediator of HlyA-induced [Ca2+]i oscillations and IL-6 release. This supports the notion that ATP signaling occurs early during bacterial infection and is a key player in the further inflammatory response. Background: The virulence factor HlyA elicits [Ca2+]i oscillations in renal epithelial cells. Results: These oscillations and following IL-6 release are reduced by inhibition or lack of P2Y2 receptors. Conclusion: The effects of HlyA in renal epithelial cells are mediated by P2Y2 receptors. Significance: ATP release and P2Y2 receptor activation are essential parts of the early interaction between Escherichia coli and the renal epithelium. |
| Databáze: | OpenAIRE |
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