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 language | English (US) |
|---|---|
| Journal | Pediatric research |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells. / Ozen, Maide; Xie, Han; Shin, Na; Al Yousif, Ghada; Clemens, Julia; McLane, Michael W.; Lei, Jun; Burd, Irina.
In: Pediatric research, 01.01.2019.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells
AU - Ozen, Maide
AU - Xie, Han
AU - Shin, Na
AU - Al Yousif, Ghada
AU - Clemens, Julia
AU - McLane, Michael W.
AU - Lei, Jun
AU - Burd, Irina
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85073825424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073825424&partnerID=8YFLogxK
U2 - 10.1038/s41390-019-0557-7
DO - 10.1038/s41390-019-0557-7
M3 - Article
C2 - 31493768
AN - SCOPUS:85073825424
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -