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Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells.
Life Sci. 2004 Jul 23; 75(10):1159-70.LS

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-kappaB) activation induced by TNF-alpha (10 ng/ml) in cultured human dermal microvascular endothelial cells (HDMEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha 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-kappaB induced by TNF-alpha 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-alpha. These findings indicate that both cell surface and mRNA expression of adhesion molecules in HDMEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappaB. These results suggest a potential therapeutic approach using antioxidant agents or nitric oxide pathway modulators in the treatment of inflammatory skin diseases.

Authors+Show Affiliations

Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15219804

Citation

Jiang, Mi-Zu, et al. "Effects of Antioxidants and Nitric Oxide On TNF-alpha-induced Adhesion Molecule Expression and NF-kappaB Activation in Human Dermal Microvascular Endothelial Cells." Life Sciences, vol. 75, no. 10, 2004, pp. 1159-70.
Jiang MZ, Tsukahara H, Ohshima Y, et al. Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells. Life Sci. 2004;75(10):1159-70.
Jiang, M. Z., Tsukahara, H., Ohshima, Y., Todoroki, Y., Hiraoka, M., Maeda, M., & Mayumi, M. (2004). Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells. Life Sciences, 75(10), 1159-70.
Jiang MZ, et al. Effects of Antioxidants and Nitric Oxide On TNF-alpha-induced Adhesion Molecule Expression and NF-kappaB Activation in Human Dermal Microvascular Endothelial Cells. Life Sci. 2004 Jul 23;75(10):1159-70. PubMed PMID: 15219804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells. AU - Jiang,Mi-Zu, AU - Tsukahara,Hirokazu, AU - Ohshima,Yusei, AU - Todoroki,Yukiko, AU - Hiraoka,Masahiro, AU - Maeda,Masayuki, AU - Mayumi,Mitsufumi, PY - 2003/11/21/received PY - 2004/01/09/accepted PY - 2004/6/29/pubmed PY - 2004/7/29/medline PY - 2004/6/29/entrez SP - 1159 EP - 70 JF - Life sciences JO - Life Sci VL - 75 IS - 10 N2 - 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-kappaB) activation induced by TNF-alpha (10 ng/ml) in cultured human dermal microvascular endothelial cells (HDMEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha 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-kappaB induced by TNF-alpha 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-alpha. These findings indicate that both cell surface and mRNA expression of adhesion molecules in HDMEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappaB. These results suggest a potential therapeutic approach using antioxidant agents or nitric oxide pathway modulators in the treatment of inflammatory skin diseases. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/15219804/Effects_of_antioxidants_and_nitric_oxide_on_TNF_alpha_induced_adhesion_molecule_expression_and_NF_kappaB_activation_in_human_dermal_microvascular_endothelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024320504004102 DB - PRIME DP - Unbound Medicine ER -