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首页> 外文期刊>Cytokine >P2X(7)R activation drives distinct IL-1 responses in dendritic cells compared to macrophages
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P2X(7)R activation drives distinct IL-1 responses in dendritic cells compared to macrophages

机译：与巨噬细胞相比，P2X（7）R激活在树突状细胞中驱动独特的IL-1反应

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The P2X(7)R is a functionally distinct member of the P2X family of non-selective cation channels associated with rapid activation of the inflammasome complex and signalling interleukin (IL)-1 beta release in macrophages. The main focus of this investigation was to compare P2X(7)R-driven IL-1 production by primary murine bone marrow derived dendritic cells (BMDC) and macrophages (BMM). P2X(7)R expression in murine BMDC and BMM at both transcriptional (P2X(7)A variant) and protein levels was demonstrated. Priming with lipopolysaccharide (LPS) and receptor activation with adenosine triphosphate (ATP) resulted in markedly enhanced IL-1 (alpha and beta) secretion in BMDC compared with BMM. In both cell types IL-1 production was profoundly inhibited with a P2X(7)R-specific inhibitor (A-740003) demonstrating that this release is predominantly a P2X(7)R-dependent process. These data also suggest that P2X(7)R and caspase-1 activation drive IL-1 alpha release from BMDC. Both cell types expressed constitutively the gain-of-function P2X(7)K as well as the full P2X(7)A variant at equivalent levels. LPS priming reduced significantly levels of P2X(7)A but not P2X(7)K transcripts in both BMDC and BMM. P2X(7)R-induced pore formation, assessed by YO-PRO-1 dye uptake, was greater in BMDC, and these cells were protected from cell death. These data demonstrate that DC and macrophages display distinct patterns of cytokine regulation, particularly with respect to IL-1, as a consequence of cell-type specific differences in the physicochemical properties of the P2X(7)R. Understanding the cell-specific regulation of these cytokines is essential for manipulating such responses in health and disease. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
机译：P2X（7）R是非选择性阳离子通道的P2X家族的功能独特成员，与炎症小体复合物的快速激活和巨噬细胞中白介素（IL）-1β的释放相关。这项研究的主要重点是比较由原代小鼠骨髓源性树突状细胞（BMDC）和巨噬细胞（BMM）产生的P2X（7）R驱动的IL-1。证明了小鼠BMDC和BMM在转录水平（P2X（7）A变体）和蛋白质水平上的P2X（7）R表达。与BMM相比，脂多糖（LPS）引发和三磷酸腺苷（ATP）激活受体导致BMDC中IL-1（α和β）分泌显着增强。在两种细胞类型中，IL-1的产生都被P2X（7）R特异性抑制剂（A-740003）强烈抑制，表明这种释放主要是P2X（7）R依赖性过程。这些数据还表明，P2X（7）R和caspase-1激活驱动IL-1α从BMDC释放。两种细胞类型都以相等的水平组成性表达功能获得性P2X（7）K以及完整的P2X（7）A变体。 LPS引发可显着降低BMDC和BMM中P2X（7）A的水平，但不降低P2X（7）K的转录水平。 P2X（7）R诱导的孔形成，通过YO-PRO-1染料摄取评估，在BMDC中更大，并且这些细胞受到保护，免受细胞死亡。这些数据表明，DC和巨噬细胞显示出不同的细胞因子调节模式，尤其是针对IL-1，这是P2X（7）R的理化特性中细胞类型特异性差异的结果。了解这些细胞因子的细胞特异性调控对于在健康和疾病中操纵此类反应至关重要。 （C）2015作者。由Elsevier Ltd.发布。这是CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）下的开放获取文章。

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