Effects of antioxidants and nitric oxide on TNF-α-induced adhesion molecule expression and NF-κB activation in human dermal microvascular endothelial cells

Mi Zu Jiang, Hirokazu Tsukahara, Yusei Ohshima, Yukiko Todoroki, Masahiro Hiraoka, Masayuki Maeda, Mitsufumi Mayumi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Cell adhesion molecules expressed on endothelial cells in inflamed skin appear to be controlled by the actions of cytokines and reactive oxygen species. However, molecular mechanisms of the expression of adhesion molecules during skin inflammation are currently not well understood. To evaluate the role of antioxidants and nitric oxide in modulating inflammatory processes in the skin, we examined the effects of pyrrolidine dithiocarbamate (PDTC, 0.1 mM) and spermine NONOate (Sper-NO, 1 mM) on adhesion molecule expression and nuclear factor kappa B (NF-κB) activation induced by TNF-α (10 ng/ml) in cultured human dermal microvascular endothelial cells (HDMEC). Treatment of cells with TNF-α for 4 h significantly induced the surface expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-α for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). The up-regulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2 h were significantly decreased by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had no significant inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-α. These findings indicate that both cell surface and mRNA expression of adhesion molecules in HDMEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-κB. These results suggest a potential therapeutic approach using antioxidant agents or nitric oxide pathway modulators in the treatment of inflammatory skin diseases.

Original languageEnglish
Pages (from-to)1159-1170
Number of pages12
JournalLife Sciences
Volume75
Issue number10
DOIs
Publication statusPublished - Jul 23 2004
Externally publishedYes

Keywords

  • Adhesion molecule
  • Endothelial activation
  • Nitric oxide
  • Nuclear factor kappa B (NF-κB)
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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