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C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells

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C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells. / Zwergal, Andreas; Quirling, Martina; Saugel, Bernd; Huth, Karin C; Sydlik, Carmen; Poli, Valeria; Neumeier, Dieter; Ziegler-Heitbrock, H W Löms; Brand, Korbinian.

In: J IMMUNOL, Vol. 177, No. 1, 01.07.2006, p. 665-72.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zwergal, A, Quirling, M, Saugel, B, Huth, KC, Sydlik, C, Poli, V, Neumeier, D, Ziegler-Heitbrock, HWL & Brand, K 2006, 'C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells', J IMMUNOL, vol. 177, no. 1, pp. 665-72.

APA

Zwergal, A., Quirling, M., Saugel, B., Huth, K. C., Sydlik, C., Poli, V., Neumeier, D., Ziegler-Heitbrock, H. W. L., & Brand, K. (2006). C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells. J IMMUNOL, 177(1), 665-72.

Vancouver

Zwergal A, Quirling M, Saugel B, Huth KC, Sydlik C, Poli V et al. C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells. J IMMUNOL. 2006 Jul 1;177(1):665-72.

Bibtex

@article{4eff3b6596ed4b86b2d96e3019e687d6,
title = "C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells",
abstract = "TNF is a major mediator of inflammation, immunity, and apoptosis. Pre-exposure to TNF reduces sensitivity to restimulation, a phenomenon known as tolerance, considered as protective in sepsis, but also as a paradigm for immunoparalysis. Earlier experiments in TNF-tolerant cells display inhibition of NF-kappaB-dependent IL-8 gene expression at the transcriptional level with potential involvement of C/EBPbeta. In this study, we have shown that a kappaB motive was sufficient to mediate transcriptional inhibition under TNF tolerance conditions in monocytic cells. Furthermore, in tolerant cells, TNF-induced NF-kappaB p65 phosphorylation was markedly decreased, which was accompanied by the formation of C/EBPbeta-p65 complexes. Remarkably, in C/EBPbeta(-/-) cells incubated under the conditions of TNF tolerance, neither impairment of transcription nor inhibition of p65 phosphorylation was observed. Finally, we showed that C/EBPbeta overexpression reduced p65-mediated transactivation and that association of C/EBPbeta with p65 specifically prevented p65 phosphorylation. Our data demonstrate that C/EBPbeta is an essential signaling component for inhibition of NF-kappaB-mediated transcription in TNF-tolerant cells and suggest that this is caused by blockade of p65 phosphorylation. These results define a new molecular mechanism responsible for TNF tolerance in monocytic cells that may contribute to the unresponsiveness seen in patients with sepsis.",
keywords = "CCAAT-Enhancer-Binding Protein-beta, Cell Line, Tumor, Gene Silencing, HeLa Cells, Humans, Immune Tolerance, Interleukin-8, Multiprotein Complexes, NF-kappa B, Phosphorylation, Promoter Regions, Genetic, Protein Subunits, Signal Transduction, Trans-Activators, Transcription Factor RelA, Transcription, Genetic, Tumor Necrosis Factor-alpha",
author = "Andreas Zwergal and Martina Quirling and Bernd Saugel and Huth, {Karin C} and Carmen Sydlik and Valeria Poli and Dieter Neumeier and Ziegler-Heitbrock, {H W L{\"o}ms} and Korbinian Brand",
year = "2006",
month = jul,
day = "1",
language = "English",
volume = "177",
pages = "665--72",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

RIS

TY - JOUR

T1 - C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells

AU - Zwergal, Andreas

AU - Quirling, Martina

AU - Saugel, Bernd

AU - Huth, Karin C

AU - Sydlik, Carmen

AU - Poli, Valeria

AU - Neumeier, Dieter

AU - Ziegler-Heitbrock, H W Löms

AU - Brand, Korbinian

PY - 2006/7/1

Y1 - 2006/7/1

N2 - TNF is a major mediator of inflammation, immunity, and apoptosis. Pre-exposure to TNF reduces sensitivity to restimulation, a phenomenon known as tolerance, considered as protective in sepsis, but also as a paradigm for immunoparalysis. Earlier experiments in TNF-tolerant cells display inhibition of NF-kappaB-dependent IL-8 gene expression at the transcriptional level with potential involvement of C/EBPbeta. In this study, we have shown that a kappaB motive was sufficient to mediate transcriptional inhibition under TNF tolerance conditions in monocytic cells. Furthermore, in tolerant cells, TNF-induced NF-kappaB p65 phosphorylation was markedly decreased, which was accompanied by the formation of C/EBPbeta-p65 complexes. Remarkably, in C/EBPbeta(-/-) cells incubated under the conditions of TNF tolerance, neither impairment of transcription nor inhibition of p65 phosphorylation was observed. Finally, we showed that C/EBPbeta overexpression reduced p65-mediated transactivation and that association of C/EBPbeta with p65 specifically prevented p65 phosphorylation. Our data demonstrate that C/EBPbeta is an essential signaling component for inhibition of NF-kappaB-mediated transcription in TNF-tolerant cells and suggest that this is caused by blockade of p65 phosphorylation. These results define a new molecular mechanism responsible for TNF tolerance in monocytic cells that may contribute to the unresponsiveness seen in patients with sepsis.

AB - TNF is a major mediator of inflammation, immunity, and apoptosis. Pre-exposure to TNF reduces sensitivity to restimulation, a phenomenon known as tolerance, considered as protective in sepsis, but also as a paradigm for immunoparalysis. Earlier experiments in TNF-tolerant cells display inhibition of NF-kappaB-dependent IL-8 gene expression at the transcriptional level with potential involvement of C/EBPbeta. In this study, we have shown that a kappaB motive was sufficient to mediate transcriptional inhibition under TNF tolerance conditions in monocytic cells. Furthermore, in tolerant cells, TNF-induced NF-kappaB p65 phosphorylation was markedly decreased, which was accompanied by the formation of C/EBPbeta-p65 complexes. Remarkably, in C/EBPbeta(-/-) cells incubated under the conditions of TNF tolerance, neither impairment of transcription nor inhibition of p65 phosphorylation was observed. Finally, we showed that C/EBPbeta overexpression reduced p65-mediated transactivation and that association of C/EBPbeta with p65 specifically prevented p65 phosphorylation. Our data demonstrate that C/EBPbeta is an essential signaling component for inhibition of NF-kappaB-mediated transcription in TNF-tolerant cells and suggest that this is caused by blockade of p65 phosphorylation. These results define a new molecular mechanism responsible for TNF tolerance in monocytic cells that may contribute to the unresponsiveness seen in patients with sepsis.

KW - CCAAT-Enhancer-Binding Protein-beta

KW - Cell Line, Tumor

KW - Gene Silencing

KW - HeLa Cells

KW - Humans

KW - Immune Tolerance

KW - Interleukin-8

KW - Multiprotein Complexes

KW - NF-kappa B

KW - Phosphorylation

KW - Promoter Regions, Genetic

KW - Protein Subunits

KW - Signal Transduction

KW - Trans-Activators

KW - Transcription Factor RelA

KW - Transcription, Genetic

KW - Tumor Necrosis Factor-alpha

M3 - SCORING: Journal article

C2 - 16785565

VL - 177

SP - 665

EP - 672

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 1

ER -