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Titolo:
Transforming growth factor-ss 1 inhibits cytokine-mediated induction of human metalloelastase in macrophages
Autore:
Feinberg, MW; Jain, MK; Werner, F; Sibinga, NES; Wiesel, P; Wang, H; Topper, JN; Perrella, MA; Lee, ME;
Indirizzi:
Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 ens Hosp, Dept Med, Boston, MA 02115 USA Brigham & Womens Hosp, Program Dev Cardiovasc Biol, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 vasc Biol, Boston, MA 02115 USA Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 ardiovasc, Boston, MA 02115 USA Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Crit Care, Boston, MA 02115 USA Stanford Univ, Sch Med, Dept Med, Div Cardiovasc, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 iv Cardiovasc, Stanford, CA 94305 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 33, volume: 275, anno: 2000,
pagine: 25766 - 25773
SICI:
0021-9258(20000818)275:33<25766:TGF1IC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; MATRIX-DEGRADING METALLOPROTEINASES; TGF-BETA; ATHEROSCLEROTIC PLAQUES; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; INCREASED EXPRESSION; STROMELYSIN GENE; SMAD PROTEINS; COLLAGENASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Feinberg, MW Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, 75 Francis St,Thorn 11, Boston, MA 02115 USA Harvard Univ 75 Francis St,Thorn 11Boston MA USA 02115 5 USA
Citazione:
M.W. Feinberg et al., "Transforming growth factor-ss 1 inhibits cytokine-mediated induction of human metalloelastase in macrophages", J BIOL CHEM, 275(33), 2000, pp. 25766-25773

Abstract

Matrix metalloproteinases (MMP) have been identified in vulnerable areas of atherosclerotic plaques and may contribute to plaque instability through extracellular matrix degradation. Human metalloelastase (MMP-12) is a macrophage-specific MMP with broad substrate specificity and is capable of degrading proteins found in the extracellular matrix of atheromas, Despite its potential importance, little is known about the regulation of MMP-12 expression in the context of atherosclerosis. In this study, we report that in human peripheral blood-derived macrophages, MMP-12 mRNA was markedly upregulated by several pro-atherosclerotic cytokines and growth factors including interleukin-1 beta, tumor necrosis factor-alpha, macrophage colony-stimulating factor, vascular endothelial growth factor, and platelet-derived growth factor-BB. In contrast, the pleiotropic anti-inflammatory growth factor transforming growth factor-beta 1 (TGF-beta 1) inhibited cytokine-mediated induction of MMP-12 mRNA, protein, and enzymatic activity. Analyses of MMP-12 promoter through transient transfections and electrophoretic mobility shift assays indicated that both its induction by cytokines and its inhibition byTGF-beta 1 depended on signaling through an AP-1 site at -81 base pairs. Moreover, the inhibitory effect of TGF-beta 1 on MMP-12 was dependent on Smad3. Taken together, MMP-12 is induced by several factors implicated in atherosclerosis. The inhibition of MMP-12 expression by TGF-beta 1 suggests that TGF-beta 1, acting via Smad3, may promote plaque stability.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 14:50:40