Hydrogen sulfide attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in vascular endothelial cells

PLoS One. 2011 May 10;6(5):e19766. doi: 10.1371/journal.pone.0019766.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelial Cells / pathology*
  • Enzyme Activation / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • NF-KappaB Inhibitor alpha
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Sulfides / pharmacology*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • U937 Cells
  • Up-Regulation / drug effects
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • I-kappa B Proteins
  • NFKBIA protein, human
  • RNA, Messenger
  • Reactive Oxygen Species
  • Sulfides
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • Heme Oxygenase-1
  • p38 Mitogen-Activated Protein Kinases
  • sodium bisulfide