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The IκB kinase complex and NF-κB act as master regulators of lipopolysaccharide-induced gene expression and control subordinate activation of AP-1

Item Type:Article
Title:The IκB kinase complex and NF-κB act as master regulators of lipopolysaccharide-induced gene expression and control subordinate activation of AP-1
Creators Name:Krappmann, D. and Wegener, E. and Sunami, Y. and Esen, M. and Thiel, A. and Mordmueller, B. and Scheidereit, C.
Abstract:Toll-like receptors (TLRs) recognize conserved products of microbial pathogens to initiate the innate immune response. TLR4 signaling is triggered upon binding of lipopolysaccharides (LPS) from gram-negative bacteria. Using comparative gene expression profiling, we demonstrate a master regulatory role of I{kappa}B kinase (IKK)/NF-{kappa}B signaling for immediate-early gene induction after LPS engagement in precursor B cells. IKK/NF-{kappa}B signaling controls a large panel of gene products associated with signaling and transcriptional activation and repression. Intriguingly, the induction of AP-1 activity by LPS in precursor B cells and primary dendritic cells fully depends on the IKK/NF-{kappa}B pathway, which promotes expression of several AP-1 family members, including JunB, JunD, and B-ATF. In pre-B cells, AP-1 augments induction of a subset of primary NF-{kappa}B targets, as shown for chemokine receptor 7 (CCR7) and immunoglobulin K light chain. Thus, our data illustrate that NF-{kappa}B orchestrates immediate-early effects of LPS signaling and controls secondary AP-1 activation to mount an appropriate biological response.
Keywords:B-Lymphocytes, Cell Line, Gene Expression Profiling, Gene Expression Regulation, I-kappa B Kinase, Immediate-Early Genes, Lipopolysaccharides, Macromolecular Substances, Molecular Sequence Data, NF-kappa B, Oligonucleotide Array Sequence Analysis, Protein-Serine-Threonine Kinases, Signal Transduction, Transcription Factor AP-1
Source:Molecular and Cellular Biology
ISSN:0270-7306
Publisher:American Society for Microbiology (U.S.A.)
Volume:24
Number:14
Page Range:6488-6500
Date:1 July 2004
Official Publication:https://doi.org/10.1128/MCB.24.14.6488-6500.2004
PubMed:View item in PubMed

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