Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFalpha. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.

Original publication

DOI

10.1038/sj.embor.7400078

Type

Journal article

Journal

EMBO Reports

Publication Date

02/2004

Volume

5

Pages

172 - 177

Addresses

Institute of Medical Microbiology and Hygiene, Philipps-University Marburg, Pilgrimstein 2, D-35037 Marburg, Germany.

Keywords

Dendritic Cells, Nucleosomes, Macrophages, Animals, Mice, Inbred BALB C, Mice, Lipopolysaccharides, Teichoic Acids, Membrane Glycoproteins, Receptors, Cell Surface, Protein Subunits, Transcription Factors, Oligodeoxyribonucleotides, Interleukin-12, Cell Culture Techniques, Signal Transduction, Genes, Reporter, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Interleukin-12 Subunit p40, Promoter Regions, Genetic