氧化型低密度脂蛋白通过 LOX-1 介导的 MAPK/NF-κB 通路刺激树突状细胞成熟。
Oxidized low-density lipoprotein stimulates dendritic cells maturation via LOX-1-mediated MAPK/NF-κB pathway.
机构信息
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
出版信息
Braz J Med Biol Res. 2021 May 31;54(9):e11062. doi: 10.1590/1414-431X2021e11062. eCollection 2021.
Dendritic cells (DCs) play a crucial role as central orchestrators of immune system response in atherosclerosis initiation and progression. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the immune maturation of DCs, but the underlying mechanisms remain unclear. We isolated mouse bone marrow progenitors and stimulated them with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce immature DCs. We then treated DCs with oxidized low-density lipoprotein (oxLDL) to induce maturation. LOX-1 siRNA was used to investigate the modulation of LOX-1 on the development of DCs and the underlying signal pathways. CD11c-positive DCs were successfully derived from mouse bone marrow progenitors. OxLDL promoted the expressions of DCs maturation markers and pro-inflammatory cytokines. OxLDL also upregulated LOX-1 expression and activated MAPK/NF-κB pathways. LOX-1 siRNA could attenuate the expression of MAPK/NF-κB pathways and inflammatory cytokines. In conclusion, oxLDL induced the maturation of DCs via LOX-1-mediated MAPK/NF-κB pathway, which contributed to the initiation and progression of atherosclerosis.
树突状细胞（DCs）在动脉粥样硬化的发生和发展中作为免疫系统反应的核心调控者发挥着至关重要的作用。凝集素样氧化型低密度脂蛋白受体-1（LOX-1）参与 DCs 的免疫成熟，但潜在机制尚不清楚。我们分离了小鼠骨髓祖细胞，并使用粒细胞巨噬细胞集落刺激因子和白细胞介素（IL）-4 刺激它们诱导未成熟的 DCs。然后，我们用氧化型低密度脂蛋白（oxLDL）处理 DCs 以诱导成熟。使用 LOX-1 siRNA 来研究 LOX-1 对 DC 发育的调节及其潜在的信号通路。成功从小鼠骨髓祖细胞中衍生出 CD11c 阳性 DCs。oxLDL 促进了 DCs 成熟标志物和促炎细胞因子的表达。oxLDL 还上调了 LOX-1 的表达并激活了 MAPK/NF-κB 通路。LOX-1 siRNA 可以减弱 MAPK/NF-κB 通路和炎症细胞因子的表达。总之，oxLDL 通过 LOX-1 介导的 MAPK/NF-κB 通路诱导 DCs 的成熟，这有助于动脉粥样硬化的发生和发展。
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