Braganhol Elizandra, Kukulski Filip, Lévesque Sébastien A, Fausther Michel, Lavoie Elise G, Zanotto-Filho Alfeu, Bergamin Leticia S, Pelletier Julie, Bahrami Fariborz, Ben Yebdri Fethia, Fonseca Moreira José Claudio, Battastini Ana Maria O, Sévigny Jean
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.
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.
Biochim Biophys Acta. 2015 Jan;1852(1):120-30. doi: 10.1016/j.bbadis.2014.10.014. Epub 2014 Oct 30.
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.
胶质瘤细胞释放细胞因子以刺激炎症，从而促进细胞增殖。在此，我们表明脂多糖（LPS）处理可诱导胶质瘤细胞增殖，且这一过程依赖于核苷酸受体激活以及白细胞介素-8（IL-8/CXCL8）分泌。我们观察到细胞外核苷酸通过激活P2X7和P2Y6受体来控制U251MG和U87MG人胶质瘤细胞系中IL-8/CXCL8以及单核细胞趋化蛋白1（MCP-1/CCL2）的释放。LPS诱导的这些细胞因子释放也受到嘌呤能受体激活的调节，因为核苷酸清除剂双磷酸酶以及药理学P2Y6受体拮抗剂苏拉明和MRS2578可降低IL-8和MCP-1的释放。与这些观察结果一致，敲低P2Y6表达可降低LPS诱导的IL-8释放以及IL-8和MCP-1的自发释放，提示核苷酸存在内源性基础释放。此外，高毫摩尔浓度的ATP可增加次优LPS浓度刺激的胶质瘤细胞中IL-8和MCP-1的释放，而这一作用可被P2X7和P2Y6拮抗剂阻断。总之，这些数据表明细胞外核苷酸通过P2受体依赖性的IL-8和MCP-1分泌来控制胶质瘤生长。
