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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.