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Titolo:
Inhibition of E-selectin gene expression by transforming growth factor beta in endothelial cells involves coactivator integration of Smad and nuclearfactor kappa B-mediated signals
Autore:
DiChiara, MR; Kiely, JM; Gimbrone, MA; Lee, ME; Perrella, MA; Topper, JN;
Indirizzi:
COR Therapeut Inc, S San Francisco, CA 94080 USA COR Therapeut Inc S San Francisco CA USA 94080 an Francisco, CA 94080 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 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Vasc Res, Boston, MA 02115 USA Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Crit Care, Boston, MA 02115 USA Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 ardiovasc, Boston, MA 02115 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 5, volume: 192, anno: 2000,
pagine: 695 - 704
SICI:
0022-1007(20000904)192:5<695:IOEGEB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
CREB-BINDING-PROTEIN; SMOOTH-MUSCLE CELLS; TGF-BETA; TRANSCRIPTIONAL ACTIVATION; TUMOR-SUPPRESSOR; RECEPTOR; P300; GROWTH-FACTOR-BETA-1; CBP/P300; PATHWAY;
Keywords:
inflammation; transcription; transforming growth factor; vascular biology; endothelium;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Topper, JN COR Therapeut Inc, 256 E Grand Ave, S San Francisco, CA 94080 USA COR Therapeut Inc 256 E Grand Ave S San Francisco CA USA 94080
Citazione:
M.R. DiChiara et al., "Inhibition of E-selectin gene expression by transforming growth factor beta in endothelial cells involves coactivator integration of Smad and nuclearfactor kappa B-mediated signals", J EXP MED, 192(5), 2000, pp. 695-704

Abstract

Transforming growth factor (TGF)-beta(1) is a pleiotropic cytokine/growth factor that is thought to play a critical role in the modulation of inflammatory events. We demonstrate that exogenous TGF-beta(1) can inhibit the expression of the proinflammatory adhesion molecule, E-selectin, in vascular endothelium exposed to inflammatory stimuli both in vitro and in vivo. This inhibitory effect occurs at the level of transcription of the E-selectin gene and is dependent on the action of Smad proteins, a class of intracellular signaling proteins involved in mediating the cellular effects of TGF-beta(1). Furthermore, we demonstrate that these Smad-mediated effects in endothelial cells result from a novel competitive interaction between Smad proteins activated by TGF-beta(1) and nuclear factor kappa B (NF kappa B) proteins activated by inflammatory stimuli (such as cytokines or bacterial lipopolysaccharide) that is mediated by the transcriptional coactivator cyclic AMPresponse element-binding protein (CREB)-binding protein (CBP). Augmentation of the Limited amount of CBP present in endothelial cells (via overexpression) or selective disruption of Smad-CBP interactions (via a dominant negative strategy) effectively antagonizes the ability of TGF-beta(1) to block proinflammatory E-selectin expression. These data thus demonstrate a novel mechanism of interaction between TGF-beta(1)-regulated Smad proteins and NFkappa B proteins regulated by inflammatory stimuli in vascular endothelialcells. This type of signaling mechanism may play an important role in the immunomodulatory actions of this cytokine/growth factor in the cardiovascular system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 08:02:10