CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by 137 can generate TCR-independent signals leading to IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-indepenclent CD28 signal leads to the selective transcription of survival (Bd-xL) and inflammatory IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of ReIA and p52 NF-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.

Marinari B., C.A. (2004). CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappa B subunits on IL-8 and Bcl-xL gene promotors. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101(16), 6098-6103 [10.1073/pnas.0308688101].

CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappa B subunits on IL-8 and Bcl-xL gene promotors

MARINARI, BARBARA;COSTANZO, ANTONIO;
2004

Abstract

CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by 137 can generate TCR-independent signals leading to IkappaB kinase and NF-kappaB activation. Here we demonstrate that the TCR-indepenclent CD28 signal leads to the selective transcription of survival (Bd-xL) and inflammatory IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-kappaB-dependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of ReIA and p52 NF-kappaB subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-kappaB sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/35 - Malattie Cutanee e Veneree
English
Con Impact Factor ISI
CD28 antigen; immunoglobulin enhancer binding protein; protein p50; protein p52; protein subunit; T lymphocyte receptor; transcription factor Rel; transcription factor RelA; apoptosis; article; b lymphocyte activation factor gene; bcl xl gene; binding site; cell protection; cell secretion; controlled study; gene; gene targeting; genetic regulation; genetic transcription; human; human cell; interleukin 2 gene; interleukin 8 gene; lymphocyte activation; priority journal; promoter region; protein binding; radiation; signal transduction; T lymphocyte; upregulation; Antigens, CD28; Base Sequence; bcl-X Protein; Biological Transport; Cell Nucleus; DNA Primers; Gene Expression Regulation; Humans; Interleukin-8; NF-kappa B; Promoter Regions (Genetics); Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Transcription Factor RelA; Transcription, Genetic
Marinari B., C.A. (2004). CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappa B subunits on IL-8 and Bcl-xL gene promotors. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101(16), 6098-6103 [10.1073/pnas.0308688101].
Marinari, B; Costanzo, A; Marzano, V; Piccolella, E; Tuosto, L
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/34253
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