Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox-LDL.
Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox-LDL.
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干预时间决定ox-LDL诱导巨噬细胞自噬、NLRP3活性和凋亡状态
DOI：
10.1186/s12944-022-01714-x
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发表时间：
2022-10-25
影响因子：
4.5
通讯作者：
Wang, Wenjian
中科院分区：
文献类型：
--
作者：
Zheng, Liang;Xu, Hongbiao;Zheng, Fufu;Lai, Yuanhui;Li, Jie;Lv, Weiming;Hu, Zuojun;Wang, Wenjian
关键词：
通过广泛的研究已经确定，自噬、含有Pyrin结构域3（NLRP 3）的核苷酸结合寡聚化结构域样受体（Nucleotide-binding oligomerization domain-like receptor）炎性体和巨噬细胞中的凋亡反应共同促成动脉粥样硬化的发生及其在脂质异常存在下的发展。很少有研究全面调查脂质异常或NLRP 3激活的干预时间是否对巨噬细胞中的自噬、NLRP 3或凋亡状态有显著影响。通过用80 μg/ml氧化低密度脂蛋白（ox-LDL）刺激THP-1单核细胞特定时间，建立人THP-1单核细胞衍生的巨噬细胞。油红O（ORO）染色观察泡沫细胞形成。蛋白质印迹法测定蛋白质表达。透射电镜和免疫荧光显微镜观察细胞自噬状态。TUNEL法检测细胞凋亡;用ox-LDL处理细胞12 h和36 h，这被认为是本研究动脉粥样硬化形成的早期和晚期阶段。结果表明，细胞松弛素D在早期抑制ox-LDL的吞噬作用，可明显改善自噬状态，降低NLRP 3的激活和凋亡反应。相比之下，细胞松弛素D对阻断晚期ox-LDL的有害作用几乎没有影响。此外，在动脉粥样硬化形成的早期和晚期阶段用靶向NLRP 3的小干扰（si）RNA治疗后，自噬、凋亡和NLRP 3表达的变化与上述数据一致。在动脉粥样硬化形成的早期或晚期阶段针对脂质紊乱或炎症反应的干预可能具有不同的结果，这取决于它们在动脉粥样硬化发病过程中何时被应用。这些结果可能有助于改善动脉粥样硬化预防的治疗策略。此外，健康的生活方式仍应被推荐为预防动脉粥样硬化的最重要和最便宜的措施。在线版本包含补充材料，可通过10.1186/s12944-022-01714-x获得。
It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages. Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data. Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis. The online version contains supplementary material available at 10.1186/s12944-022-01714-x.
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影响因子：
4.4
作者：
Karasawa T;Takahashi M
通讯作者：
Takahashi M
DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
影响因子：
20.1
作者：
Libby P;Hansson GK
通讯作者：
Hansson GK
影响因子：
9.3
作者：
Almeida, Shone O.;Budoff, Matthew
通讯作者：
Budoff, Matthew
影响因子：
20.3
作者：
Berberich, Amanda J.;Hegele, Robert A.
通讯作者：
Hegele, Robert A.