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中性细胞细胞外陷形成模型由酸和甲酸诱导:参与MAPK信号通路

Chenxi Wu¹, Xinru Xu¹, Yueyue Shi¹

¹School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

International journal of molecular sciences

|January 11, 2025

概括

单酸盐 (MSU) 和醇12-米酸盐13-酸盐 (PMA) 通过依赖于活性氧物种 (ROS) 的Ras-Raf-ERK通路诱导中性粒细胞外陷 (NETs) 的形成. 这一发现为水晶相关的炎症性疾病 (如痛风) 提供了潜在的治疗点.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

中性细胞外细胞陷 (NETs) 在痛风等炎症状况中至关重要,但它们的形成机制尚未完全理解.
单酸盐 (MSU) 晶体是痛风性关节炎中NET形成的关键触发因素.

研究的目的:

建立一个模型来研究由MSU和博12-米里13-酸盐 (PMA) 诱导的NET形成.
阐明涉及MSU和PMA诱导的NET形成的分子途径.

主要方法:

激光共聚焦显微镜用于NET可视化.
流细胞计用于检测活性氧物种 (ROS).
传输电子显微镜用于中性粒细胞微观结构.
西方涂抹用于蛋白质表达分析.
对向MAPK通路 (Ras,Raf,ERK,p38) 的抑制剂,NADPH氧化酶和中性粒细胞弹性酶的评估.

主要成果:

MSU和PMA显著诱导了NET形成,增加了ROS,乳酸脱酶释放,dsDNA和IL-8.
拉斯-拉夫-ERK通路,NADPH氧化酶 (DPI) 和中性粒细胞弹性酶 (Alvelestat) 的抑制剂有效降低了NET形成指标.
p38 MAPK 抑制剂 (SB203580) 并没有显著影响 NET 形成.

结论:

涉及Ras-Raf-ERK的信号通路,依赖于ROS,对于MSU和PMA诱导的NET形成至关重要.
这些发现突出了治疗水晶诱导的炎症性疾病,特别是痛风的潜在分子标.
这项研究为开发针对NET相关病理的新型治疗策略提供了基础.

关键词:

在 MAPK 信号通道中.单尿酸盐是一种酸盐.中性粒细胞外细胞陷佛博尔米里斯酸乙酸.

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