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Open Access Research article

Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts

Agnes Lovas1, Dörte Radke256, Daniela Albrecht3, Z Buket Yilmaz14, Ulrich Möller2, Andreas JR Habenicht5 and Falk Weih1*

Author Affiliations

1 Research Group Immunology, Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany

2 Bioinformatics – Pattern Recognition, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany

3 Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany

4 Signal Transduction in Tumor Cells, Max Delbrück Center for Molecular Medicine, Robert Rössle Strasse 10, 13092 Berlin-Buch, Germany

5 Institute for Vascular Medicine, Friedrich Schiller University of Jena, Bachstrasse 18, 07743 Jena, Germany

6 Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Walther Rathenau Strasse 48, 17475 Greifswald, Germany

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BMC Genomics 2008, 9:606  doi:10.1186/1471-2164-9-606

Published: 16 December 2008

Abstract

Background

Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described, the classical inhibitor of NF-κB α (IκBα)-regulated and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-κB heterodimers, respectively.

Results

Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryonic fibroblasts (MEFs) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that were regulated by RelA and/or RelB. The majority of LTβR-regulated genes required the presence of both RelA and RelB, revealing significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, LTβR activation inhibited expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (pparg), suggesting that LTβR signaling may interfere with adipogenic differentiation.

Conclusion

Microarray analysis of LTβR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB.