A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Abstract Text:

J T Cooper,D M Stroka,C Brostjan,A Palmetshofer,F H Bach,C Ferran,

The A20 gene product is a novel zinc finger protein originally described as a tumor necrosis factor alpha (TNF)-inducible early response gene in human umbilical vein endothelial cells (HUVEC). Its described function is to block TNF-induced apoptosis in fibroblasts and B lymphocytes, but more recently it has also been shown to play a role in lymphoid cell maturation. The mechanism of action of A20 is unknown. The aim of our study was to assess the effect of A20 upon endothelial cell activation. By transfecting bovine aortic endothelial cells (BAEC) with A20 as well as reporter constructs consisting of the promoters of genes known to be up-regulated during endothelial cell activation, i.e. E-selectin, interleukin (IL)-8, tissue factor (TF), and inhibitor of nuclear factor kappaBalpha (IkappaBalpha), we demonstrate that A20 expression inhibits gene up-regulation associated with TNF, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), and hydrogen peroxide (H2O2)-induced endothelial cell (EC) activation. The mechanism of action of A20 is in part, or totally, due to the blockade of nuclear factor kappaB (NF-kappaB), as shown by its ability to suppress the activity of a NF-kappaB reporter. This effect is specific, as A20 does not block a noninducible, constitutively expressed reporter, Rous sarcoma virus-luciferase (RSV-LUC); nor does it block the c-Tat-inducible, NF-kappaB-independent reporter, human immunodeficiency virus-chloramphenicol acetyltransferase (HIV-CAT). How A20 blocks NF-kappaB is unclear, although we demonstrate that it does not affect p65 (RelA)-mediated gene transactivation. The inhibition of endothelial cell activation by A20 is a novel function for A20.

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Publishing Authors By Initials

JT Cooper,DM Stroka,C Brostjan,A Palmetshofer,FH Bach,C Ferran,

For similar zinc fingers research abstracts see: zinc fingers research

PUBMED ID PMID:

MEDLINE DATE:

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 271

Page Numbers: 18068-73

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 26

MONTH: Jul

YEAR: 1996

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Keywords Mesh Terms:

KEYWORDS: Zinc Fingers

MESH TERMS: metabolism

Chemical & Substance for Abstract: A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Information

Substance Name: TNFAIP3 protein, human

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.

AFFILIATION: Sandoz Center for Immunobiology, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.

Country: UNITED STATES

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism Related Publications

• A novel function for A20 in smooth muscle cells: inhibition of activation and proliferation.
• A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.
• A20 inhibits cytokine-induced apoptosis and nuclear factor kappaB-dependent gene activation in islets.
• A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.
• A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis.
• A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis.
• A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.
• A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and induces regression of neointimal hyperplasia.
• Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells.
• Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.
• Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function.
• Management of acute and chronic ankle instability.
• The graft unveils its secrets: provocative therapeutic leads to protected vascularized allografts.
• The universal NF-kappaB inhibitor a20 protects from transplant vasculopathy by differentially affecting apoptosis in endothelial and smooth muscle cells.
• [Not Available.]