Effects of antioxidants and NO on TNF-α-induced adhesion molecule expression in human pulmonary microvascular endothelial cells

Mi Zu Jiang, Hirokazu Tsukahara, Kazuyo Hayakawa, Yukiko Todoroki, Satoshi Tamura, Yusei Ohshima, Masahiro Hiraoka, Mitsufumi Mayumi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-α signaling and upregulate gene expression. We therefore evaluated 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 pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-α for 4 h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-α for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyclic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2 h were decreased significantly by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-α. Treatment with TNF-α for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-κB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung.

Original languageEnglish
Pages (from-to)580-591
Number of pages12
JournalRespiratory Medicine
Volume99
Issue number5
DOIs
Publication statusPublished - May 2005
Externally publishedYes

Fingerprint

E-Selectin
Intercellular Adhesion Molecule-1
Endothelial Cells
Antioxidants
Lung
Up-Regulation
Vascular Cell Adhesion Molecule-1
NF-kappa B
Messenger RNA
S-Nitroso-N-Acetylpenicillamine
Cytokines
Acetylcysteine
Endothelium
Blood Vessels
Leukocytes
Oxygen
Gene Expression
prolinedithiocarbamate
Therapeutics

Keywords

  • Cytokine
  • Endothelial activation
  • Human
  • Pulmonary inflammation
  • Reactive oxygen intermediates

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effects of antioxidants and NO on TNF-α-induced adhesion molecule expression in human pulmonary microvascular endothelial cells. / Jiang, Mi Zu; Tsukahara, Hirokazu; Hayakawa, Kazuyo; Todoroki, Yukiko; Tamura, Satoshi; Ohshima, Yusei; Hiraoka, Masahiro; Mayumi, Mitsufumi.

In: Respiratory Medicine, Vol. 99, No. 5, 05.2005, p. 580-591.

Research output: Contribution to journalArticle

Jiang, Mi Zu ; Tsukahara, Hirokazu ; Hayakawa, Kazuyo ; Todoroki, Yukiko ; Tamura, Satoshi ; Ohshima, Yusei ; Hiraoka, Masahiro ; Mayumi, Mitsufumi. / Effects of antioxidants and NO on TNF-α-induced adhesion molecule expression in human pulmonary microvascular endothelial cells. In: Respiratory Medicine. 2005 ; Vol. 99, No. 5. pp. 580-591.
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AU - Jiang, Mi Zu

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AU - Todoroki, Yukiko

AU - Tamura, Satoshi

AU - Ohshima, Yusei

AU - Hiraoka, Masahiro

AU - Mayumi, Mitsufumi

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N2 - Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-α signaling and upregulate gene expression. We therefore evaluated 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 pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-α for 4 h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-α for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyclic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2 h were decreased significantly by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-α. Treatment with TNF-α for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-κB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung.

AB - Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-α signaling and upregulate gene expression. We therefore evaluated 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 pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-α for 4 h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-α for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyclic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2 h were decreased significantly by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-α. Treatment with TNF-α for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-κB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung.

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