Magnesium sulfate inhibits binding of lipopolysaccharide to THP-1 cells by reducing expression of cluster of differentiation 14

We investigated effects of magnesium sulfate (MgSO₄) 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 MgSO₄ (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 MgSO₄ significantly inhibits LPS–macrophage binding and mCD14 expression. Notably, these effects of MgSO₄ 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 MgSO₄ significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO₄ on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO₄ inhibits LPS–macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.