Modulatory effect of magnesium sulfate on NLRP3 inflammasome expression by human monocytes stimulated in vitro with monosodium urate

Abstract

The NLRP3 inflammasome contributes to inflammation in preeclampsia (PE), a hypertensive pregnancy disorder associated with immune imbalance. Magnesium sulfate (MgSO₄), the standard therapy for eclampsia, also exhibits anti-inflammatory properties linked to intracellular calcium regulation. This study investigated the modulatory effect of MgSO₄ on NLRP3 inflammasome expression in monocytes from 16 healthy non-pregnant women stimulated with monosodium urate (MSU). Monocytes were cultured in vitro with or without MSU and MgSO₄. Gene and protein expression of NLRP3, caspase-1, and gasdermin D were assessed by RT-qPCR and flow cytometry. The concentrations of IL-1β, IL-18, TNF-α, and IL-10 in culture supernatants were measured using ELISA. MSU stimulation increased the expression of NLRP3 and its components, confirming the activation of the inflammasome. Treatment with MgSO₄ significantly reduced the expression of NLRP3, caspase-1, gasdermin D, IL-1β, and TNF-α, while increasing IL-10 levels. Additionally, MSU induced intracellular calcium elevation, whereas MgSO₄ significantly decreased calcium concentration. These findings demonstrate that MgSO₄ exerts an immunomodulatory effect on MSU-activated monocytes by downregulating NLRP3 inflammasome activation, pyroptosis, and proinflammatory cytokine production through a calcium-dependent mechanism. This suggests that MgSO₄ may contribute to reducing the exaggerated inflammatory response associated with PE, supporting its therapeutic actions beyond seizure prevention.