High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.
High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.
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高密度脂蛋白（HDL）介导逆向胆固醇转运，已知对动脉粥样硬化有保护作用。此外，高密度脂蛋白具有有效的抗炎特性，可能对预防其他炎症性疾病至关重要。高密度脂蛋白如何调节炎症的分子机制，特别是免疫细胞如巨噬细胞，仍然知之甚少。在这里，我们发现转录抑制因子ATF3作为巨噬细胞中hdl诱导的靶基因，下调toll样受体（TLR）诱导的促炎细胞因子的表达。在体内和体外，HDL对tlr诱导炎症的保护作用完全依赖于ATF3。我们的发现可以解释HDL广泛的抗炎和代谢作用，并为预测新的基于HDL的治疗方法的成功提供基础。
High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies.