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Molecular and Cellular Biology, July 2004, p. 6488-6500, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6488-6500.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The I{kappa}B Kinase Complex and NF-{kappa}B Act as Master Regulators of Lipopolysaccharide-Induced Gene Expression and Control Subordinate Activation of AP-1

Daniel Krappmann,1* Elmar Wegener,1 Yoshiaki Sunami,1 Meral Esen,2 Andreas Thiel,2 Benjamin Mordmuller,1,{dagger} and Claus Scheidereit1

Max Delbrück Center for Molecular Medicine, D-13122 Berlin,1 Deutsches Rheuma-Forschungszentrum Berlin, 10117 Berlin,Germany2

Received 4 March 2004/ Accepted 21 April 2004

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 {kappa} 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.

* Corresponding author. Mailing address: Max Delbrück Center for Molecular Medicine, MDC, Robert Rössle Str. 10, D-13122 Berlin, Germany. Phone: 49-30-9406-3751. Fax: 49-30-9406-3866. E-mail: dkrapp{at}mdc-berlin.de.

{dagger} Present address: Department of Parasitology, University of Tübingen, 72074 Tübingen, Germany.

Molecular and Cellular Biology, July 2004, p. 6488-6500, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6488-6500.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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