| TLR2- and nucleotide-binding oligomerization domain 2-dependent Krüppel-like factor 2 expression downregulates NF-kappa B-related gene expression. | |
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MedLine Citation:
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PMID: 20525885 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The release of potent proinflammatory mediators is not only central for mounting an efficient host response, but also bears the risk for deleterious excessive tissue-damaging inflammation. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance between a robust inflammatory response to kill pneumococci and loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krüppel-like factor (KLF)2 counterregulates pneumococci- and pattern recognition receptor-related human lung cell activation. Pneumococci induced KLF2 expression in vitro and in a murine pneumonia model. Activation of TLR2- and nucleotide-binding oligomerization domain protein 2-related signaling induced KLF2 expression in a PI3K-dependent manner. Overexpression of KLF2 downregulated pneumococci-, TLR2-, and nucleotide-binding oligomerization domain protein 2-related NF-kappaB-dependent gene expression and IL-8 release, whereas small interfering RNA-based silencing of KLF2 provoked an enhanced inflammatory response. KLF2-dependent downregulation of NF-kappaB activity is partly reversible by overexpression of the histone acetylase p300/CREB-binding protein-associated factor. In conclusion, KLF2 may act as a counterregulatory transcription factor in pneumococci- and pattern recognition receptor-related proinflammatory activation of lung cells, thereby preventing lung hyperinflammation and subsequent organ failure. |
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Authors:
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Janine Zahlten; Robert Steinicke; Bastian Opitz; Julia Eitel; Philippe Dje N'guessan; Maya Vinzing; Martin Witzenrath; Bernd Schmeck; Sven Hammerschmidt; Norbert Suttorp; Stefan Hippenstiel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-04 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-09-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 597-604 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité University Medicine Berlin, Berlin, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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physiology Animals Cell Line Disease Models, Animal Down-Regulation / genetics, immunology* Gene Expression Regulation / immunology* Humans Inflammation Mediators / antagonists & inhibitors, metabolism, physiology* Kruppel-Like Transcription Factors / biosynthesis*, genetics, physiology* Mice Multiple Organ Failure / genetics, immunology, prevention & control NF-kappa B p50 Subunit / antagonists & inhibitors*, genetics, metabolism Nod2 Signaling Adaptor Protein / physiology* Pneumonia, Pneumococcal / genetics, immunology*, prevention & control Streptococcus pneumoniae / immunology Toll-Like Receptor 2 / biosynthesis, genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Card15 protein, mouse; 0/Inflammation Mediators; 0/Klf2 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/NF-kappa B p50 Subunit; 0/Nod2 Signaling Adaptor Protein; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2; 147257-52-1/Nfkb1 protein, mouse; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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