title: Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFkappaB pathway.
abstract: Dysfunctional endothelial cell activation and cytokines are implicated in preterm labor, a condition commonly treated with the tocolytic agent, magnesium sulfate (MgSO(4)). Based on recent findings showing the inflammatory effects of magnesium deficiency, we examined the effect of MgSO(4) on human umbilical vein endothelial cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical cords were incubated with MgSO(4) prior to stimulation with lipopolysaccharide (LPS) and then assessed for endothelial cell activation. Endothelial cell supernatants were assayed for inflammatory mediator production (interleukin-8; IL-8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1) expression was determined. In the absence of LPS stimulation, MgSO(4) had no effect on HuVEC responses. Treatment of HuVECs with MgSO(4) prior to LPS stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies showed that MgSO(4) reduced NFkappaB nuclear translocation and protected cytoplasmic IkappaBalpha from degradation in LPS-treated HuVECs. In conclusion, MgSO(4) inhibits endothelial cell activation, as measured by levels of IL-8 and ICAM-1 expression, via NFkappaB. Our results support the hypothesis that MgSO(4) treatment may function as an anti-inflammatory agent during preterm labor.
authors.affiliation: Division of Maternal-Fetal Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Burton
authors.initials: B
authors.lastname: Rochelson
authors.affiliation: The Susan & Herman Merinoff Center for Patient Oriented Research, The Feinstein Institute for Medical Research North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Oonagh
authors.initials: O
authors.lastname: Dowling
authors.affiliation: Division of Maternal-Fetal Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Schwartz
authors.affiliation: The Susan & Herman Merinoff Center for Patient Oriented Research, The Feinstein Institute for Medical Research North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: cmetz@nshs.edu.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Metz
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology*; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology / Q000473:pathology; D015149:Tocolytic Agents / Q000494:pharmacology*; D014471:Umbilical Veins / Q000276:immunology* / Q000473:pathology
chemical_list: C508606:CXCL8 protein, human; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D015149:Tocolytic Agents; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D008278:Magnesium Sulfate