Cargando…
Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency
Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-κB and MAP kinase...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118688/ https://www.ncbi.nlm.nih.gov/pubmed/17724128 http://dx.doi.org/10.1084/jem.20070183 |
_version_ | 1782141084631040000 |
---|---|
author | Yamamoto, Masahiro Uematsu, Satoshi Okamoto, Toru Matsuura, Yoshiharu Sato, Shintaro Kumar, Himanshu Satoh, Takashi Saitoh, Tatsuya Takeda, Kiyoshi Ishii, Ken J. Takeuchi, Osamu Kawai, Taro Akira, Shizuo |
author_facet | Yamamoto, Masahiro Uematsu, Satoshi Okamoto, Toru Matsuura, Yoshiharu Sato, Shintaro Kumar, Himanshu Satoh, Takashi Saitoh, Tatsuya Takeda, Kiyoshi Ishii, Ken J. Takeuchi, Osamu Kawai, Taro Akira, Shizuo |
author_sort | Yamamoto, Masahiro |
collection | PubMed |
description | Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-κB and MAP kinases, as well as gene expression in vitro. To clarify the physiological function of Trib1 in TLR-mediated responses, we generated Trib1-deficient mice by gene targeting. Microarray analysis showed that Trib1-deficient macrophages exhibited a dysregulated expression pattern of lipopolysaccharide-inducible genes, whereas TLR-mediated activation of MAP kinases and NF-κB was normal. Trib1 was found to associate with NF-IL6 (also known as CCAAT/enhancer-binding protein β). NF-IL6–deficient cells showed opposite phenotypes to those in Trib1-deficient cells in terms of TLR-mediated responses. Moreover, overexpression of Trib1 inhibited NF-IL6–dependent gene expression by down-regulating NF-IL6 protein expression. In contrast, Trib1-deficient cells exhibited augmented NF-IL6 DNA-binding activities with increased amounts of NF-IL6 proteins. These results demonstrate that Trib1 is a negative regulator of NF-IL6 protein expression and modulates NF-IL6–dependent gene expression in TLR-mediated signaling. |
format | Text |
id | pubmed-2118688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21186882008-03-03 Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency Yamamoto, Masahiro Uematsu, Satoshi Okamoto, Toru Matsuura, Yoshiharu Sato, Shintaro Kumar, Himanshu Satoh, Takashi Saitoh, Tatsuya Takeda, Kiyoshi Ishii, Ken J. Takeuchi, Osamu Kawai, Taro Akira, Shizuo J Exp Med Articles Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-κB and MAP kinases, as well as gene expression in vitro. To clarify the physiological function of Trib1 in TLR-mediated responses, we generated Trib1-deficient mice by gene targeting. Microarray analysis showed that Trib1-deficient macrophages exhibited a dysregulated expression pattern of lipopolysaccharide-inducible genes, whereas TLR-mediated activation of MAP kinases and NF-κB was normal. Trib1 was found to associate with NF-IL6 (also known as CCAAT/enhancer-binding protein β). NF-IL6–deficient cells showed opposite phenotypes to those in Trib1-deficient cells in terms of TLR-mediated responses. Moreover, overexpression of Trib1 inhibited NF-IL6–dependent gene expression by down-regulating NF-IL6 protein expression. In contrast, Trib1-deficient cells exhibited augmented NF-IL6 DNA-binding activities with increased amounts of NF-IL6 proteins. These results demonstrate that Trib1 is a negative regulator of NF-IL6 protein expression and modulates NF-IL6–dependent gene expression in TLR-mediated signaling. The Rockefeller University Press 2007-09-03 /pmc/articles/PMC2118688/ /pubmed/17724128 http://dx.doi.org/10.1084/jem.20070183 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Yamamoto, Masahiro Uematsu, Satoshi Okamoto, Toru Matsuura, Yoshiharu Sato, Shintaro Kumar, Himanshu Satoh, Takashi Saitoh, Tatsuya Takeda, Kiyoshi Ishii, Ken J. Takeuchi, Osamu Kawai, Taro Akira, Shizuo Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title | Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title_full | Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title_fullStr | Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title_full_unstemmed | Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title_short | Enhanced TLR-mediated NF-IL6–dependent gene expression by Trib1 deficiency |
title_sort | enhanced tlr-mediated nf-il6–dependent gene expression by trib1 deficiency |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118688/ https://www.ncbi.nlm.nih.gov/pubmed/17724128 http://dx.doi.org/10.1084/jem.20070183 |
work_keys_str_mv | AT yamamotomasahiro enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT uematsusatoshi enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT okamototoru enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT matsuurayoshiharu enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT satoshintaro enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT kumarhimanshu enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT satohtakashi enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT saitohtatsuya enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT takedakiyoshi enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT ishiikenj enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT takeuchiosamu enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT kawaitaro enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency AT akirashizuo enhancedtlrmediatednfil6dependentgeneexpressionbytrib1deficiency |