Neutrophil extracellular traps induce IL-1β production by macrophages in combination with lipopolysaccharide.
Neutrophil extracellular traps induce IL-1β production by macrophages in combination with lipopolysaccharide.
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DOI：
10.3892/ijmm.2017.2870
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发表时间：
2017-03
影响因子：
5.4
通讯作者：
Nagaoka I
中科院分区：
文献类型：
--
作者：
Hu Z;Murakami T;Tamura H;Reich J;Kuwahara-Arai K;Iba T;Tabe Y;Nagaoka I
暴露于入侵微生物后，中性粒细胞会发生 NETosis（一种最近发现的程序性细胞死亡类型），并释放中性粒细胞胞外陷阱 (NET)。 NET 被描述为一种抗菌机制，因为 NET 可以捕获微生物并通过 NET 相关成分的作用表现出杀菌活性。相比之下，NET 的成分已被认为是损伤相关分子模式分子 (DAMP)，它会触发炎症信号，从而诱导细胞死亡、炎症和器官衰竭。在本研究中，为了阐明 NET 对巨噬细胞产生细胞因子的影响，用 NET 与脂多糖 (LPS) 结合作为病原体相关分子模式的组成部分处理小鼠巨噬细胞样 J774 细胞。结果表明，在 LPS 存在的情况下，NETs 显着诱导 J774 细胞产生白细胞介素 (IL)-1β。值得注意的是，NET/LPS 诱导的 IL-1β 产生受到 caspase-1 和 caspase-8 抑制剂的抑制。此外，核酸酶和丝氨酸蛋白酶抑制剂（而非抗组蛋白抗体）显着抑制 NET/LPS 诱导的 IL-1β 产生。此外，我们证实caspase-1和caspase-8被NETs/LPS激活，并且LPS、DNA和中性粒细胞弹性蛋白酶的组合在重建实验中诱导IL-1β的产生。这些观察结果表明，NET 通过 caspase-1 和 caspase-8 途径诱导 J774 巨噬细胞与 LPS 结合产生 IL-1β，并且 NET 相关 DNA 和丝氨酸蛋白酶作为必要成分参与 NET/LPS 诱导的 IL-1β 产生。
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NET-associated components. In contrast, the components of NETs have been recognized as damage-associated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure. In the present study, to clarify the effect of NETs on cytokine production by macrophages, mouse macrophage-like J774 cells were treated with NETs in combination with lipopolysaccharide (LPS) as a constituent of pathogen-associated molecular patterns. The results revealed that NETs significantly induced the production of interleukin (IL)-1β by J774 cells in the presence of LPS. Notably, the NET/LPS-induced IL-1β production was inhibited by both caspase-1 and caspase-8 inhibitors. Furthermore, nucleases and serine protease inhibitors but not anti-histone antibodies significantly inhibited the NET/LPS-induced IL-1β production. Moreover, we confirmed that caspase-1 and caspase-8 were activated by NETs/LPS, and the combination of LPS, DNA and neutrophil elastase induced IL-1β production in reconstitution experiments. These observations indicate that NETs induce the production of IL-1β by J774 macrophages in combination with LPS via the caspase-1 and caspase-8 pathways, and NET-associated DNA and serine proteases are involved in NET/LPS-induced IL-1β production as essential components.