Abstract
Background:
Hydrogen sulfide (H(2)S), the third physiologically relevant gaseous molecule, is recognized increasingly as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H(2)S donor) on tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) dysfunction.
Methodology and principal findings:
Application of NaHS concentration-dependently suppressed TNF-α-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of NaHS. Furthermore, TNF-α-induced NF-κB activation assessed by IκBα degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS.
Significance:
H(2)S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up-regulation of HO-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Adhesion / drug effects
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Endothelial Cells / drug effects*
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Endothelial Cells / enzymology
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Endothelial Cells / pathology*
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Enzyme Activation / drug effects
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / metabolism
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Humans
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I-kappa B Proteins / metabolism
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Inflammation / metabolism*
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Inflammation / pathology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Intracellular Space / drug effects
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Intracellular Space / metabolism
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NF-KappaB Inhibitor alpha
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Protein Transport / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects*
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Sulfides / pharmacology*
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Transcription Factor RelA / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
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U937 Cells
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Up-Regulation / drug effects
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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I-kappa B Proteins
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NFKBIA protein, human
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RNA, Messenger
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Reactive Oxygen Species
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Sulfides
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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NF-KappaB Inhibitor alpha
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Heme Oxygenase-1
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p38 Mitogen-Activated Protein Kinases
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sodium bisulfide