This study was designed to explore the protective effect of D4F, an apolipoprotein A-I mimetic peptide, on nuclear factor-κB (NF-κB)-dependent Fas/Fas ligand (FasL) pathway-mediated apoptosis in macrophages induced by oxidized low-density lipoprotein (ox-LDL). Our results showed that ox-LDL induced apoptosis, NF-κB P65 nuclear translocation and the upregulation of Fas/FasL pathway-related proteins, including Fas, FasL, Fas-associated death domain proteins (FADD), caspase-8 and caspase-3 in RAW264.7 macrophages, whereas silencing of Fas blocked ox-LDL-induced macrophage apoptosis. Furthermore, silencing of P65 attenuated macrophage apoptosis and the upregulation of Fas caused by ox-LDL, whereas P65 expression was not significantly affected by treatment with Fas siRNA. D4F attenuated the reduction of cell viability and the increase in lactate dehydrogenase leakage and apoptosis. Additionally, D4F inhibited ox-LDL-induced P65 nuclear translocation and upregulation of Fas/FasL pathway-related proteins in RAW264.7 cells and in atherosclerotic lesions of apoE^-/- mice. However, Jo2, a Fas-activating monoclonal antibody, reversed the inhibitory effect of D4F on ox-LDL-induced cell apoptosis and upregulation of Fas, FasL and FADD. These data indicate that NF-κB mediates Fas/FasL pathway activation and apoptosis in macrophages induced by ox-LDL and that D4F protects macrophages from ox-LDL-induced apoptosis by suppressing the activation of NF-κB and the Fas/FasL pathway.

中文翻译：

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D4F通过抑制依赖于NF-κB的Fas / FasL途径来减轻巨噬细胞衍生的泡沫细胞凋亡。

这项研究旨在探讨载脂蛋白AI模拟肽D4F对氧化低密度脂蛋白诱导的巨噬细胞中核因子-κB（NF-κB）依赖性Fas / Fas配体（FasL）途径介导的细胞凋亡的保护作用（ox-LDL）。我们的研究结果表明，ox-LDL诱导细胞凋亡，NF-κBP65核易位以及Fas / FasL途径相关蛋白的上调，包括Fas，FasL，Fas相关死亡域蛋白（FADD），caspase-8和caspase-3在RAW264.7巨噬细胞中，Fas沉默可阻止ox-LDL诱导的巨噬细胞凋亡。此外，P65沉默可减弱由ox-LDL引起的巨噬细胞凋亡和Fas的上调，而P65表达不受Fas siRNA处理的影响不明显。D4F减弱了细胞活力的降低以及乳酸脱氢酶渗漏和凋亡的增加。此外，D4F抑制ox-LDL诱导的P65核易位以及RAW264.7细胞和apoE动脉粥样硬化病变中Fas / FasL途径相关蛋白的上调^-/-老鼠。然而，Jos，一种Fas活化单克隆抗体，逆转了D4F对ox-LDL诱导的细胞凋亡以及Fas，FasL和FADD上调的抑制作用。这些数据表明，NF-κB介导了由ox-LDL诱导的巨噬细胞中Fas / FasL途径的激活和凋亡，而D4F通过抑制NF-κB和Fas / FasL途径的激活来保护巨噬细胞免受ox-LDL诱导的凋亡的影响。