Nucleotide receptors control IL-8/CXCL8 and MCP-1/CCL2 secretions as well as proliferation in human glioma cells.

Abstract

Glioma cells release cytokines to stimulate inflammation that facilitates cell proliferation. Here, we show that Lipopolysaccharide (LPS) treatment could induce glioma cells to proliferate and this process was dependent on nucleotide receptor activation as well as interleukin-8 (IL-8/CXCL8) secretion. We observed that extracellular nucleotides controlled IL-8/CXCL8 and monocyte chemoattractant protein 1 (MCP-1/CCL2) release by U251MG and U87MG human glioma cell lines via P2X7 and P2Y6 receptor activation. The LPS-induced release of these cytokines was also modulated by purinergic receptor activation since IL-8 and MCP-1 release was decreased by the nucleotide scavenger apyrase as well as by the pharmacological P2Y6 receptor antagonists suramin and MRS2578. In agreement with these observations, the knockdown of P2Y6 expression decreased LPS-induced IL-8 release as well as the spontaneous release of IL-8 and MCP-1, suggesting an endogenous basal release of nucleotides. Moreover, high millimolar concentrations of ATP increased IL-8 and MCP-1 release by the glioma cells stimulated with suboptimal LPS concentration which were blocked by P2X7 and P2Y6 antagonists. Altogether, these data suggest that extracellular nucleotides control glioma growth via P2 receptor-dependent IL-8 and MCP-1 secretions.

• Authors: Elizandra Braganhol, Filip Kukulski, Sébastien A Lévesque, Michel Fausther, Elise G Lavoie, Alfeu Zanotto-Filho, Leticia S Bergamin, Julie Pelletier, Fariborz Bahrami, Fethia Ben Yebdri, José Claudio Fonseca Moreira, Ana Maria O Battastini, Jean Sévigny
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1852 Issue 1 Pg. 120-30 (Jan 2015) ISSN: 0006-3002 [Print] Netherlands
• PMID: 25445541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• CCL2 protein, human
• CXCL8 protein, human
• Chemokine CCL2
• DNA Primers
• Interleukin-8
• Receptors, Purinergic

Topics

• Base Sequence
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Chemokine CCL2 (metabolism)
• DNA Primers
• Glioma (metabolism, pathology)
• Humans
• Interleukin-8 (metabolism)
• Polymerase Chain Reaction
• Receptors, Purinergic (genetics, metabolism, physiology)
• Signal Transduction