Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan.
Department of Anesthesiology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Inflammopharmacology. 2019 Apr;27(2):249-260. doi: 10.1007/s10787-019-00568-7. Epub 2019 Feb 5.
We investigated effects of magnesium sulfate (MgSO) on modulating lipopolysaccharide (LPS)-macrophage binding and cluster of differentiation 14 (CD14) expression. Flow cytometry data revealed that the mean levels of LPS-macrophage binding and membrane-bound CD14 expression (mCD14) in differentiated THP-1 cells (a human monocytic cell line) treated with LPS plus MgSO (the LPS + M group) decreased by 28.2% and 25.3% compared with those THP-1 cells treated with LPS only (the LPS group) (P < 0.001 and P = 0.037), indicating that MgSO significantly inhibits LPS-macrophage binding and mCD14 expression. Notably, these effects of MgSO were counteracted by L-type calcium channel activation. Moreover, the mean level of soluble CD14 (sCD14; proteolytic cleavage product of CD14) in the LPS + M group was 25.6% higher than in the LPS group (P < 0.001), indicating that MgSO significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO inhibits LPS-macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.
我们研究了硫酸镁(MgSO)对调节脂多糖(LPS)-巨噬细胞结合和分化抗原 14(CD14)表达的影响。流式细胞术数据显示,用 LPS 和 MgSO(LPS+M 组)处理的分化 THP-1 细胞(一种人单核细胞系)中 LPS-巨噬细胞结合和膜结合 CD14 表达(mCD14)的平均水平分别降低了 28.2%和 25.3%,与仅用 LPS 处理的 THP-1 细胞(LPS 组)相比(P<0.001 和 P=0.037),表明 MgSO 可显著抑制 LPS-巨噬细胞结合和 mCD14 表达。值得注意的是,MgSO 的这些作用被 L 型钙通道激活所拮抗。此外,LPS+M 组中可溶性 CD14(sCD14;CD14 的蛋白水解裂解产物)的平均水平比 LPS 组高 25.6%(P<0.001),表明 MgSO 可显著增强 CD14 的蛋白水解裂解。值得注意的是,丝氨酸蛋白酶抑制减轻了 MgSO 对降低 mCD14 和增加 sCD14 的作用。总之,MgSO 通过减少 CD14 表达来抑制 LPS-巨噬细胞结合。其机制可能涉及拮抗 L 型钙通道和激活丝氨酸蛋白酶。