| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B-Dependent Gene Expression in TLR4-Stimulated Dendritic Cells Exposed to Genistein1
,
* Laboratory for Eukaryotic Gene Expression and Signal Transduction (LEGEST), Molecular Biology, Ghent University, Ghent, Belgium;
Institute for Medical Immunology, Faculty of Medecine, Free University of Brussels, Charleroi-Gosselies, Belgium;
Laboratory for Molecular Cancer Biology, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, Ghent, Belgium; and
Laboratory of Molecular Embryology, Free University of Brussels, Charleroi-Gosselies, Belgium
Considerable research has focused on the anti-inflammatory and antiproliferative activities exhibited by the soy isoflavone genistein. We previously demonstrated that genistein suppresses TNF-
-induced NF-
B-dependent IL-6 gene expression in cancer cells by interfering with the mitogen- and stress-activated protein kinase 1 activation pathway. However, effects of isoflavones on immune cells, such as dendritic cells, remain largely unknown. Here we show that genistein markedly reduces IL-6 cytokine production and transcription in LPS-stimulated human monocyte-derived dendritic cells. More particularly, we observe that genistein inhibits IL-6 gene expression by modulating the transcription factor NF-B. Examination of NF-B-related events downstream of TLR4 demonstrates that genistein affects NF-B subcellular localization and DNA binding, although we observe only a minor inhibitory impact of genistein on the classical LPS-induced signaling steps. Interestingly, we find that genistein significantly increases p53 protein levels. We also show that overexpression of p53 in TLR4/MD2 HEK293T cells blocks LPS-induced NF-B-dependent gene transcription, indicating the occurrence of functional cross-talk between p53 and NF-B. Moreover, analysis of IL-6 mRNA levels in bone marrow-derived p53 null vs wild-type dendritic cells confirms a role for p53 in the reduction of NF-B-dependent gene expression, mediated by genistein.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Interuniversitaire Attractiepolen p5/12 and the Geconcerteerde Onderzoeksacties. N.D. is a fellow with the Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen. S.Go., S.Ge, and S.F. are postdoctoral researchers of the Fonds National de la Recherche Scientifique, V.A. is supported by Interuniversity Attraction Pole of the Belgian Federal Science Policy, and S.G. and W.V.B. are postdoctoral fellows with the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen.
2 Address correspondence and reprint requests to Dr. Wim Vanden Berghe, Laboratory for Eukaryotic Gene Expression and Signal Transduction, Molecular Biology, K. L. Ledeganckstraat 35, Ghent, Belgium. E-mail address: w.vandenberghe{at}ugent.be
3 Abbreviations used in this paper: DC, dendritic cell; MoDC, monocyte-derived DC; BMDC, bone marrow-derived DC; IKK, IB kinase; h, human; HEK, human embryonic kidney; fw, forward; rv, reverse; REA, restriction enzyme accessibility assay; gDNA, genomic DNA; poly(IC), polyinosinic-polycytidylic acid; MSK1, mitogen- and stress-activated protein kinase 1; RNAi, RNA interference.
This article has been cited by other articles:
|
|
 |
|
  M. N. Ndlovu, C. Van Lint, K. Van Wesemael, P. Callebert, D. Chalbos, G. Haegeman, and W. Vanden Berghe Hyperactivated NF-{kappa}B and AP-1 Transcription Factors Promote Highly Accessible Chromatin and Constitutive Transcription across the Interleukin-6 Gene Promoter in Metastatic Breast Cancer Cells Mol. Cell. Biol., October 15, 2009; 29(20): 5488 - 5504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. LUST, B. VANHOECKE, M. VAN GELE, J. BOELENS, H. VAN MELCKEBEKE, M. KAILEH, W. VANDEN BERGHE, G. HAEGEMAN, J. PHILIPPE, M. BRACKE, et al. Xanthohumol Activates the Proapoptotic Arm of the Unfolded Protein Response in Chronic Lymphocytic Leukemia Anticancer Res, October 1, 2009; 29(10): 3797 - 3805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Liu, Y.-J. Park, Y. Tsuruta, E. Lorne, and E. Abraham p53 Attenuates Lipopolysaccharide-Induced NF-{kappa}B Activation and Acute Lung Injury J. Immunol., April 15, 2009; 182(8): 5063 - 5071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, C. A. Ghiani, J. Y. Kim, A. Liu, J. Sandoval, J. DeVellis, and P. Casaccia-Bonnefil Inhibition of p53 Transcriptional Activity: A Potential Target for Future Development of Therapeutic Strategies for Primary Demyelination J. Neurosci., June 11, 2008; 28(24): 6118 - 6127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Secchiero, F. Corallini, E. Rimondi, C. Chiaruttini, M. G. di Iasio, A. Rustighi, G. Del Sal, and G. Zauli Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells Blood, February 1, 2008; 111(3): 1287 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. P. Ng, D. S. Nin, J. H. Fong, D. Venkataraman, C.-S. Chen, and M. Khan Therapeutic targeting of nuclear receptor corepressor misfolding in acute promyelocytic leukemia cells with genistein Mol. Cancer Ther., August 1, 2007; 6(8): 2240 - 2248. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
