title: 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.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Elizandra
authors.initials: E
authors.lastname: Braganhol
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Filip
authors.initials: F
authors.lastname: Kukulski
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Sébastien A
authors.initials: SA
authors.lastname: Lévesque
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Fausther
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Elise G
authors.initials: EG
authors.lastname: Lavoie
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Alfeu
authors.initials: A
authors.lastname: Zanotto-Filho
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Bergamin
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Bahrami
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada.
authors.forename: Fethia
authors.initials: F
authors.lastname: Ben Yebdri
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: José Claudio
authors.initials: JC
authors.lastname: Fonseca Moreira
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil. Electronic address: abattastini@gmail.com.
authors.forename: Ana Maria O
authors.initials: AM
authors.lastname: Battastini
authors.affiliation: Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec, CHUL, Québec, QC G1V 4G2, Canada. Electronic address: jean.sevigny@crchul.ulaval.ca.
authors.forename: Jean
authors.initials: J
authors.lastname: Sévigny
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism*; D017931:DNA Primers; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D017931:DNA Primers; D016209:Interleukin-8; D011983:Receptors, Purinergic
keywords: ATP; Glioma; IL-8/CXCL8; MCP-1/CCL2; P2 receptor