Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Mediators Inflamm. 2018 Dec 17;2018:8907143. doi: 10.1155/2018/8907143. eCollection 2018.
We previously reported that propofol upregulated the expression of ATP-binding cassette transporter subfamily A member 1 (ABCA1) via peroxisome proliferator-activated receptor gamma/liver X receptor in macrophage-derived foam cells. Here, we provide evidence that in addition to inducing ABCA1 expression, propofol represses proinflammatory cytokine production by increasing ABCA1 expression in a LOC286367-dependent manner. Western blot analysis showed that ABCA1 expression was elevated in macrophages by propofol treatment and this effect was markedly reduced by LOC286367 overexpression. Moreover, propofol treatment downregulated the production of the proinflammatory cytokines interleukin-6, tumor necrosis factor, and interferon gamma in lipopolysaccharide-stimulated macrophages by enhancing ABCA1 expression. Notably, propofol achieved this effect in a LOC286367-dependent manner. To the best of our knowledge, this is the first report of the mechanism in which propofol represses proinflammatory cytokine production mediated by ABCA1.
我们之前的研究表明，丙泊酚通过过氧化物酶体增殖物激活受体γ/肝 X 受体在上皮细胞源性泡沫细胞中上调 ABCA1 的表达。在这里，我们提供的证据表明，除了诱导 ABCA1 表达外，丙泊酚还通过增加 ABCA1 的表达来抑制炎症细胞因子的产生，这一过程依赖于 LOC286367。Western blot 分析表明，丙泊酚处理可使巨噬细胞中 ABCA1 的表达升高，而 LOC286367 的过表达则明显降低了这一作用。此外，丙泊酚通过增强 ABCA1 的表达，下调脂多糖刺激的巨噬细胞中促炎细胞因子白细胞介素 6、肿瘤坏死因子和干扰素 γ的产生。值得注意的是，丙泊酚在 LOC286367 依赖的方式下实现了这一效应。据我们所知，这是丙泊酚通过 ABCA1 抑制炎症细胞因子产生的机制的首次报道。
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