Atherosclerosis, a chronic inflammatory disease of the arterial wall, is the leading cause of cardiac disorders and stroke. The onset and progression of these diseases are linked with the inflammatory response, especially NLRP3 inflammasome activation, inducing the production of proinflammatory cytokines, such as interleukin 1β (IL-1β). Because high-density lipoproteins (HDLs) have shown significant antiatherogenic and anti-inflammatory properties, we evaluated their immunomodulatory activity in response to cholesterol crystals and other innate immune activators. Human primary monocyte-derived macrophages, THP-1 cells, and murine macrophages were stimulated to activate NLRP3 inflammasome and other pattern recognition receptors, in the presence or absence of HDL. Then, HDL immunomodulatory effects were evaluated through IL-1β and IL-6 production by enzyme-linked immunosorbent assay. Furthermore, in vivo HDL anti-inflammatory effects were evaluated in a murine model of peritoneal inflammatory infiltration. HDLs have an immunomodulatory effect on different cellular models, including peripheral blood mononuclear cells, THP-1 cells, and murine macrophages, by affecting the activity of innate immunity sensors, such as Toll-like receptors (TLRs), dectin-1, and inflammasomes. HDL reduces the proinflammatory role of cholesterol crystals, nigericin, and other NLRP3 and AIM2 inflammasome agonists, and several TLR agonists, leading to a decreased production of IL-1β and IL-6. The results suggest that HDLs are highly important in the regulation of the innate immune response and may have a beneficial role in controlling diseases associated with the inflammatory response.

中文翻译：

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高密度脂蛋白降低促炎活性并调节先天免疫反应。

动脉粥样硬化，一种动脉壁的慢性炎性疾病，是心脏疾病和中风的主要原因。这些疾病的发作和发展与炎症反应有关，尤其是NLRP3炎性体的激活，从而诱导促炎细胞因子如白介素1β（IL-1β）的产生。因为高密度脂蛋白（HDL）已显示出显着的抗动脉粥样硬化和抗炎特性，所以我们评估了它们对胆固醇晶体和其他先天性免疫激活剂的免疫调节活性。在存在或不存在HDL的情况下，刺激人原代单核细胞衍生的巨噬细胞，THP-1细胞和鼠巨噬细胞激活NLRP3炎性体和其他模式识别受体。然后，通过酶联免疫吸附试验通过IL-1β和IL-6的产生来评估HDL的免疫调节作用。此外，在小鼠腹膜炎性浸润模型中评估了体内HDL的抗炎作用。HDL通过影响先天性免疫传感器（例如Toll样受体（TLR），dectin-1和炎症小体）的活性，对不同的细胞模型（包括外周血单核细胞，THP-1细胞和鼠巨噬细胞）具有免疫调节作用。HDL降低了胆固醇晶体，尼日利亚霉素和其他NLRP3和AIM2炎性体激动剂以及几种TLR激动剂的促炎作用，从而导致IL-1β和IL-6的产生减少。