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Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals.
Arterioscler Thromb. 1994 Oct; 14(10):1665-73.AT

Abstract

Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha (TNF) is due to induction of surface receptors, such as vascular cell adhesion molecule-1 (VCAM-1). The antioxidant pyrrolidine dithiocarbamate (PDTC) specifically inhibits activation of nuclear factor-kappa B (NF-kappa B). Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) promoters, we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM-1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein endothelial cells (HUVECs). PDTC or N-acetylcysteine dose dependently reduced TNF-induced VCAM-1 but not ICAM-1 surface protein (also in human umbilical arterial endothelial cells) and mRNA expression (by 70% at 100 mumol/L PDTC) in HUVECs as assessed by flow cytometry and polymerase chain reaction. Gel-shift analysis in HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF, suggesting that only VCAM-1 induction was controlled by NF-kappa B. Since HUVECs released superoxide anions in response to TNF, and H2O2 induces VCAM-1, PDTC may act as a radical scavenger. Although ICAM-1 induction was unaffected, inhibitors of NADPH oxidase (apocynin) or cytochrome P-450 (SKF525a) suppressed VCAM-1 induction by TNF, revealing that several radical-generating systems are involved in its regulation. PDTC, apocynin, or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs (by 75% at 100 mumol/L PDTC). Inhibition by anti-VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Institut für Prophylaxe der Kreislaufkrankheiten, München, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7522548

Citation

Weber, C, et al. "Antioxidants Inhibit Monocyte Adhesion By Suppressing Nuclear Factor-kappa B Mobilization and Induction of Vascular Cell Adhesion Molecule-1 in Endothelial Cells Stimulated to Generate Radicals." Arteriosclerosis and Thrombosis : a Journal of Vascular Biology, vol. 14, no. 10, 1994, pp. 1665-73.
Weber C, Erl W, Pietsch A, et al. Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. Arterioscler Thromb. 1994;14(10):1665-73.
Weber, C., Erl, W., Pietsch, A., Ströbel, M., Ziegler-Heitbrock, H. W., & Weber, P. C. (1994). Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. Arteriosclerosis and Thrombosis : a Journal of Vascular Biology, 14(10), 1665-73.
Weber C, et al. Antioxidants Inhibit Monocyte Adhesion By Suppressing Nuclear Factor-kappa B Mobilization and Induction of Vascular Cell Adhesion Molecule-1 in Endothelial Cells Stimulated to Generate Radicals. Arterioscler Thromb. 1994;14(10):1665-73. PubMed PMID: 7522548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. AU - Weber,C, AU - Erl,W, AU - Pietsch,A, AU - Ströbel,M, AU - Ziegler-Heitbrock,H W, AU - Weber,P C, PY - 1994/10/1/pubmed PY - 1994/10/1/medline PY - 1994/10/1/entrez SP - 1665 EP - 73 JF - Arteriosclerosis and thrombosis : a journal of vascular biology JO - Arterioscler Thromb VL - 14 IS - 10 N2 - Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha (TNF) is due to induction of surface receptors, such as vascular cell adhesion molecule-1 (VCAM-1). The antioxidant pyrrolidine dithiocarbamate (PDTC) specifically inhibits activation of nuclear factor-kappa B (NF-kappa B). Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) promoters, we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM-1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein endothelial cells (HUVECs). PDTC or N-acetylcysteine dose dependently reduced TNF-induced VCAM-1 but not ICAM-1 surface protein (also in human umbilical arterial endothelial cells) and mRNA expression (by 70% at 100 mumol/L PDTC) in HUVECs as assessed by flow cytometry and polymerase chain reaction. Gel-shift analysis in HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF, suggesting that only VCAM-1 induction was controlled by NF-kappa B. Since HUVECs released superoxide anions in response to TNF, and H2O2 induces VCAM-1, PDTC may act as a radical scavenger. Although ICAM-1 induction was unaffected, inhibitors of NADPH oxidase (apocynin) or cytochrome P-450 (SKF525a) suppressed VCAM-1 induction by TNF, revealing that several radical-generating systems are involved in its regulation. PDTC, apocynin, or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs (by 75% at 100 mumol/L PDTC). Inhibition by anti-VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 1049-8834 UR - https://www.unboundmedicine.com/medline/citation/7522548/Antioxidants_inhibit_monocyte_adhesion_by_suppressing_nuclear_factor_kappa_B_mobilization_and_induction_of_vascular_cell_adhesion_molecule_1_in_endothelial_cells_stimulated_to_generate_radicals_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=7522548.ui DB - PRIME DP - Unbound Medicine ER -