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

Research output: Contribution to journalArticle

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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Purinergic P2X7 Receptors
Magnesium Sulfate
Human Umbilical Vein Endothelial Cells
Interleukin-1
Inflammation
Adenosine Triphosphate
Anti-Inflammatory Agents
Divalent Cations
Premature Birth
Magnesium
Down-Regulation
Cell Culture Techniques
Apoptosis
Messenger RNA

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 journalArticle

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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.",
author = "Maide Ozen and Han Xie and Na Shin and {Al Yousif}, Ghada and Julia Clemens and McLane, {Michael W.} and Jun Lei and Irina Burd",
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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.

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