Magnesium sulfate enhances lipopolysaccharide tolerance

Abstract

Introduction Lipopolysaccharide (LPS) tolerance is the downregulation of LPS signaling after pre-exposure to LPS, and it provides protection against hyperactive inflammation. Cytokine production decreases during LPS tolerance, and the phenotype of LPS-tolerant monocytes shifts toward M2 (anti-inflammatory) type. Magnesium sulfate (MgSO 4 ) is a widely used anti-inflammatory agent. Although MgSO 4 inhibits LPS signaling, the effect of MgSO 4 on LPS tolerance is unknown. In the present study, we investigated the in vitro effects of MgSO 4 on LPS tolerance. Methods To induce LPS tolerance, THP-1 cells were stimulated with LPS (200 ng/mL, 2 h) after pre-exposure to LPS (200 ng/mL, 24 h) with or without pre-treatment of MgSO 4 (20 mM, 24 h). Results Our results revealed that MgSO 4 enhanced LPS tolerance by downregulating nuclear factor-κB (NF-κB)-induced tumor necrosis factor-α or interleukin-6, and upregulating cluster of differentiation 163 (a M2-associated marker). Furthermore, the LPS-triggered upregulation of phosphoinositide 3-kinase (PI3K) was significantly increased during LPS tolerance. MgSO 4 activated PI3K, but inhibited NF-κB in LPS-stimulated cells. Notably, MgSO 4 mitigated the signaling of both PI3K and NF-κB in LPS-tolerant cells, suggesting the effect of MgSO 4 on LPS tolerance relies on the modulation of the crosstalk between PI3K and NF-κB. Conclusion MgSO 4 enhanced LSP tolerance, thus providing evidence for a novel underlying mechanism of the anti-inflammatory effects of MgSO 4 .