Electronegative LDL (LDL(-)) and free fatty acids (FFAs) are circulating risk factors for cardiovascular diseases (CVDs) and have been associated with inflammation. Interleukin-1 beta (IL-1β) represents a key cytokine in the development of CVD; however, the initial trigger of IL-1β in CVD remains to be explored. In this study, we investigated the combined effects of LDL(-) from the plasma of ST-segment elevation myocardial infarction (STEMI) patients or diet-induced hypercholesterolemic rabbits and bovine serum albumin bound palmitic acid (PA-BSA) on IL-1β production in macrophages. Macrophages derived from THP-1 cells or human peripheral blood mononuclear cells were independently treated with LDL(-), PA-BSA or cotreated with LDL(-) and PA-BSA. The results showed that nLDL and/or PA-BSA had no effect on IL-1β, and LDL(-) slightly increased IL-1β; however, cotreatment with LDL(-) and PA-BSA resulted in abundant secretion of IL-1β in macrophages. Rabbit LDL(-) induced the elevation of cellular pro-IL-1β and p-Iκ-Bα, but PA-BSA had no effect on pro-IL-1β or p-Iκ-Bα. In potassium-free buffer, LDL(-)-induced IL-1β reached a level similar to that induced by cotreatment with LDL(-) and PA-BSA. Moreover, LDL(-) and PA-BSA-induced IL-1β was inhibited in lectin-type oxidized LDL receptor-1 (LOX-1) knockdown cells and by blockers of voltage-gated potassium (Kv) channels. LDL(-) from diet-induced hypercholesterolemic rabbit had a similar effect as STEMI LDL(-) on IL-1β in macrophages. These results show that PA-BSA cooperates with LDL(-) to trigger IL-1β production in macrophages via a mechanism involving the LOX-1 and Kv channel pathways, which may play crucial roles in the regulation of inflammation in CVD.

负电性低密度脂蛋白 (LDL(-)) 和游离脂肪酸 (FFA) 是心血管疾病 (CVD) 的循环危险因素，并且与炎症有关。白介素 1 β (IL-1β) 是 CVD 发展中的关键细胞因子；然而，IL-1β 在 CVD 中的最初触发因素仍有待探索。在本研究中，我们研究了 ST 段抬高型心肌梗死 (STEMI) 患者或饮食诱导的高胆固醇血症兔血浆中的 LDL(-) 和牛血清白蛋白结合棕榈酸 (PA-BSA) 对 IL-1β 的联合影响巨噬细胞中产生。将源自THP-1细胞或人外周血单核细胞的巨噬细胞单独用LDL(-)、PA-BSA处理或用LDL(-)和PA-BSA共同处理。结果显示nLDL和/或PA-BSA对IL-1β没有影响，LDL(-)轻微增加IL-1β；然而，LDL(-)和PA-BSA共同处理导致巨噬细胞大量分泌IL-1β。兔LDL(-)诱导细胞pro-IL-1β和p-Iκ-Bα升高，但PA-BSA对pro-IL-1β和p-Iκ-Bα没有影响。在无钾缓冲液中，LDL(-)诱导的IL-1β达到了与LDL(-)和PA-BSA共同处理相似的水平。此外，在凝集素型氧化LDL受体1（LOX-1）敲低细胞中，LDL（-）和PA-BSA诱导的IL-1β受到电压门控钾（Kv）通道阻滞剂的抑制。来自饮食诱导的高胆固醇血症兔的 LDL(-) 对巨噬细胞中 IL-1β 的影响与 STEMI LDL(-) 相似。这些结果表明，PA-BSA通过涉及LOX-1和Kv通道途径的机制与LDL(-)协同触发巨噬细胞中IL-1β的产生，这可能在CVD炎症的调节中发挥重要作用。