Abstract

Apolipoprotein A-I (ApoA-I) is a key component of reverse cholesterol transport in humans. In the previous studies, we demonstrated expression of the apoA-I gene in human monocytes and macrophages; however, little is known on the regulation of the apoA-I expression in macrophages during the uptake of modified low-density lipoprotein (LDL), which is one of the key processes in the early stages of atherogenesis leading to formation of foam cells. Here, we demonstrate a complex nature of the apoA-I regulation in human macrophages during the uptake of oxidized LDL (oxLDL). Incubation of macrophages with oxLDL induced expression of the apoA-I gene within the first 24 hours, but suppressed it after 48 h. Both effects depended on the interaction of oxLDL with the TLR4 receptor, rather than on the oxLDL uptake by the macrophages. The oxLDL-mediated downregulation of the apoA-I gene depended on the ERK1/2 and JNK cascades, as well as on the NF-κB cascade.

中文翻译：

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氧化低密度脂蛋白对人类巨噬细胞载脂蛋白 AI 基因表达的调控

摘要

载脂蛋白 AI (ApoA-I) 是人类胆固醇逆向转运的关键组成部分。在之前的研究中，我们证明了apoA-I基因在人类单核细胞和巨噬细胞中的表达。然而，关于修饰低密度脂蛋白（LDL）摄取过程中巨噬细胞中apoA-I表达的调节知之甚少，这是导致泡沫细胞形成的动脉粥样硬化早期阶段的关键过程之一。在这里，我们展示了人类巨噬细胞在氧化 LDL (oxLDL) 摄取过程中apoA-I调节的复杂性质。用oxLDL孵育巨噬细胞诱导apoA-的表达I 在最初的 24 小时内基因，但在 48 小时后抑制它。这两种作用都取决于oxLDL与TLR4受体的相互作用，而不是巨噬细胞对oxLDL的摄取。oxLDL 介导的apoA-I基因下调依赖于 ERK1/2 和 JNK 级联，以及 NF-κB 级联。