Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells

Maide Ozen, Han Xie, Na Shin, Ghada Al Yousif, Julia Clemens, Michael W. McLane, Jun Lei, Irina Burd

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Abstract

Background: Magnesium sulfate (MgSO4) is utilized for fetal neuroprotection in preterm birth but its mechanism of action is still poorly understood. P2X7 receptor (P2X7R) is required for secretion of IL-1β, and can be blocked by divalent cations such as magnesium (Mg) and its own antagonist, Brilliant Blue G (BBG). We sought to determine whether during inflammation MgSO4 can block endothelial IL-1β secretion, using an in-vitro model. Methods: Human umbilical vein endothelial cell (HUVEC) cultures were treated with varying doses of LPS, 2′(3)-Ο-(4-Benzoylbenzoyl) adenosine-5′-triphosphate (BzATP), BBG and MgSO4 for 3- or 24 h. We determined cell cytotoxicity, apoptosis, IL-1β mRNA expression, IL-1β production and secretion and P2X7R expression on HUVECs. Results: We demonstrated that MgSO4 is efficacious in blocking IL-1β-mediated-inflammation in HUVECs, at both the initiation and propagation phases of inflammation. MgSO4 exerts these anti-inflammatory effects via downregulation of P2X7Rs on HUVECs. Conclusion: LPS-exposure increases IL-1β production and secretion in HUVECs, which is further intensified by P2X7R agonist, BzATP while MgSO4 inhibits IL-1β in both presence and absence of BzATP. This effect is similar to the results of P2X7R antagonist, BBG, suggesting that the anti-inflammatory effects of MgSO4 is through P2X7R.

Original languageEnglish (US)
JournalPediatric research
DOIs
StateAccepted/In press - Jan 1 2019

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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