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 language | English |
|---|---|
| Pages (from-to) | 580-591 |
| Number of pages | 12 |
| Journal | Respiratory Medicine |
| Volume | 99 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2005 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Effects of antioxidants and NO on TNF-α-induced adhesion molecule expression in human pulmonary microvascular endothelial cells
AU - Jiang, Mi Zu
AU - Tsukahara, Hirokazu
AU - Hayakawa, Kazuyo
AU - Todoroki, Yukiko
AU - Tamura, Satoshi
AU - Ohshima, Yusei
AU - Hiraoka, Masahiro
AU - Mayumi, Mitsufumi
PY - 2005/5
Y1 - 2005/5
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.
KW - Cytokine
KW - Endothelial activation
KW - Human
KW - Pulmonary inflammation
KW - Reactive oxygen intermediates
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UR - http://www.scopus.com/inward/citedby.url?scp=16344363846&partnerID=8YFLogxK
U2 - 10.1016/j.rmed.2004.10.007
DO - 10.1016/j.rmed.2004.10.007
M3 - Article
VL - 99
SP - 580
EP - 591
JO - Respiratory Medicine
JF - Respiratory Medicine
SN - 0954-6111
IS - 5
ER -