Document Detail


TLR2- and nucleotide-binding oligomerization domain 2-dependent Krüppel-like factor 2 expression downregulates NF-kappa B-related gene expression.
MedLine Citation:
PMID:  20525885     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-04
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  597-604     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité University Medicine Berlin, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / 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:
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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