P2Y14 receptor activation decreases interleukin-6 production and glioma GL261 cell proliferation in microglial transwell cultures.
P2Y14 receptor activation decreases interleukin-6 production and glioma GL261 cell proliferation in microglial transwell cultures.
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DOI：
10.1007/s11060-017-2700-9
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发表时间：
2018-03
影响因子：
3.9
通讯作者：
Watters JJ
中科院分区：
文献类型：
--
作者：
Curet MA;Watters JJ
神经胶质瘤富含细胞外核苷酸，其调节神经胶质瘤细胞产生多种细胞因子，包括白细胞介素（IL）-6，其强烈促进神经胶质瘤细胞增殖。然而，很少有人知道核苷酸信号如何调节小胶质细胞/巨噬细胞（MG/MP）细胞因子的产生在神经胶质瘤的背景下，也没有MG/MP嘌呤能P2受体表达的变化在肿瘤微环境。我们假设：1）关键P2 Y受体的表达将在胶质瘤衍生的MG/MP中增强，和2）这些受体在体外的选择性活化将调节IL-6的小胶质细胞产生和胶质瘤细胞增殖。我们使用鼠GL 261胶质瘤模型测试这些假设。与从正常脑组织分离的MG/MP相比，从GL 261肿瘤分离的CD 11b+细胞表达更高水平的几种P2受体，包括P2 Y14受体。为了评估小胶质细胞P2 Y14受体在肿瘤细胞中的功能，我们首先在具有GL 261细胞的transwell中培养N9小胶质细胞，并且发现小胶质细胞P2 Y14 mRNA水平在transwell培养物中类似地增加。GL 261细胞在单独培养或与N9细胞在transwell培养中均不表达可检测的P2 Y14水平。用UDP-葡萄糖（UDPG）选择性激活P2 Y14受体不影响单独培养的任一细胞类型中的IL-6水平，但在transwell培养物中，UDPG降低培养基中的IL-6蛋白水平。UDPG处理的小胶质细胞的条件培养基的应用降低了GL 261细胞的增殖。总之，这些数据表明，P2 Y14受体可能是参与肿瘤环境中胶质瘤细胞-MG/MP通讯的关键受体。
Gliomas are rich in extracellular nucleotides that modulate glioma cell production of multiple cytokines including interleukin (IL)-6, which strongly contributes to glioma cell proliferation. However, little is known about how nucleotide signaling modulates microglial/macrophage (MG/MP) cytokine production in the context of gliomas, nor how MG/MP purinergic P2 receptor expression changes in the tumor micro-environment. We hypothesized that: 1) expression of key P2Y receptors will be augmented in glioma-derived MG/MP, and 2) selective activation of these receptors in vitro will regulate microglial production of IL-6 and glioma cell proliferation. We tested these hypotheses using the murine GL261 glioma model. Compared to MG/MP isolated from the normal brain tissue, CD11b+ cells isolated from GL261 tumors expressed higher levels of several P2 receptors, including P2Y14 receptors. To evaluate microglial P2Y14 receptor function in the context of tumor cells, we first cultured N9 microglia in transwells with GL261 cells and found that microglial P2Y14 mRNA levels were similarly increased in transwell cultures. GL261 cells did not express detectable P2Y14 levels either when they were cultured alone or in transwell cultures with N9 cells. Selective P2Y14 receptor activation with UDP-glucose (UDPG) did not affect IL-6 levels in either cell type cultured alone, but in transwell cultures, UDPG decreased IL-6 protein levels in the medium. Application of conditioned medium from UDPG-treated microglia reduced GL261 cell proliferation. Together, these data suggest that P2Y14 receptors may be a key a receptor involved in glioma cell-MG/MP communication in the tumor environment.
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影响因子：
7.3
作者：
Kreda, S. M.;Seminario-Vidal, L.;Lazarowski, E. R.
通讯作者：
Lazarowski, E. R.
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