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10.1038/s41390-019-0557-7

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suck abstract from ncbi


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pmid31493768
      Pediatr+Res 2020 ; 87 (3 ): 463-471
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  • Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells #MMPMID31493768
  • Ozen M ; Xie H ; Shin N ; Al Yousif G ; Clemens J ; McLane MW ; Lei J ; Burd I
  • Pediatr Res 2020[Feb]; 87 (3 ): 463-471 PMID31493768 show ga
  • BACKGROUND: Magnesium sulfate (MgSO(4)) 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-1?, 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 MgSO(4) can block endothelial IL-1? secretion, using an in-vitro model. METHODS: Human umbilical vein endothelial cell (HUVEC) cultures were treated with varying doses of LPS, 2'(3)-?-(4-Benzoylbenzoyl) adenosine-5'-triphosphate (BzATP), BBG and MgSO(4) for 3- or 24?h. We determined cell cytotoxicity, apoptosis, IL-1? mRNA expression, IL-1? production and secretion and P2X7R expression on HUVECs. RESULTS: We demonstrated that MgSO(4) is efficacious in blocking IL-1?-mediated-inflammation in HUVECs, at both the initiation and propagation phases of inflammation. MgSO(4) exerts these anti-inflammatory effects via downregulation of P2X7Rs on HUVECs. CONCLUSION: LPS-exposure increases IL-1? production and secretion in HUVECs, which is further intensified by P2X7R agonist, BzATP while MgSO(4) inhibits IL-1? 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 MgSO(4) is through P2X7R.
  • |Anti-Inflammatory Agents/*pharmacology [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Human Umbilical Vein Endothelial Cells/*drug effects/metabolism/pathology [MESH]
  • |Humans [MESH]
  • |Inflammation/metabolism/pathology/*prevention & control [MESH]
  • |Interleukin-1beta/metabolism [MESH]
  • |Magnesium Sulfate/*pharmacology [MESH]
  • |Purinergic P2X Receptor Antagonists/*pharmacology [MESH]
  • |Receptors, Purinergic P2X7/*drug effects/metabolism [MESH]
  • |Secretory Pathway [MESH]


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