Unidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain.
Int J Mol Sci. 2020 Jun 30;21(13):4686. doi: 10.3390/ijms21134686.
The release of nucleotides during necrosis or apoptosis has been described to have both proinflammatory and anti-inflammatory effect on the surrounding cells. Here we describe how low concentrations of UTP and ATP applied during macrophage priming enhance IL-1β production when subsequently the NLRP3 inflammasome is activated in murine resident peritoneal macrophages. Deficiency or pharmacological inhibition of the purinergic receptor P2Y reverted the increase of IL-1β release induced by nucleotides. IL-1β increase was found dependent on the expression of gene and probably involving JNK activity. On the contrary, nucleotides decreased the production of a different proinflammatory cytokines such as TNF-α. These results suggest that nucleotides could shape the response of macrophages to obtain a unique proinflammatory signature that might be relevant in unrevealing specific inflammatory conditions.
在坏死或细胞凋亡过程中核苷酸的释放被描述为对周围细胞具有促炎和抗炎作用。在这里，我们描述了低浓度的 UTP 和 ATP 在巨噬细胞初始激活时如何增强随后激活 NLRP3 炎性体时的 IL-1β 产生。嘌呤能受体 P2Y 的缺乏或药理学抑制使核苷酸诱导的 IL-1β 释放增加得到逆转。发现 IL-1β 的增加依赖于 基因的表达，可能涉及 JNK 活性。相反，核苷酸会减少不同促炎细胞因子（如 TNF-α）的产生。这些结果表明，核苷酸可以塑造巨噬细胞对获得独特的促炎特征的反应，这在揭示特定炎症条件方面可能具有重要意义。
