Department of Biochemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minamitamagaki, Suzuka 513-8670, Japan.
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi 5, Yamashina, Kyoto 607-8414, Japan.
Int J Mol Sci. 2024 Aug 11;25(16):8757. doi: 10.3390/ijms25168757.
Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis, as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16-24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, and H3K14ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.
中性粒细胞胞外诱捕网（NET）的形成已被确定为一种新的细胞死亡介质，称为 NETosis，它与细胞凋亡和坏死不同。NET 通过将 DNA 释放到细胞外环境中，捕获外来物质，如细菌，并与炎症性疾病和改变的免疫反应有关。短链脂肪酸（如乙酸盐）是由肠道微生物群产生的，并据报道增强先天免疫反应；然而，其潜在的分子机制尚不清楚。在这里，我们通过关注与中性粒细胞样 HL-60 细胞中组蛋白乙酰化相关的机制，研究了血液和胃肠道中乙酸盐浓度最高的乙酸钠对 NETosis 的影响。乙酸钠通过用 SYTOX 绿进行荧光染色增强了 NETosis，并且该效果与处理时间（16-24 小时）直接成正比。此外，添加乙酸钠显著增强了 Ace-H3、H3K9ace 和 H3K14ace 的乙酰化。当用钙离子载体 A23187 刺激时，乙酸钠诱导的组蛋白乙酰化迅速降低，而组蛋白瓜氨酸化明显增加。这些结果表明，乙酸钠通过中性粒细胞样 HL-60 细胞中的组蛋白乙酰化诱导 NETosis，为基于膳食纤维增强先天免疫的治疗效果提供了新的见解。
