DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands
End C, Bikker F, Renner M, Bergmann G, Lyer S, Blaich S, Hudler M, Helmke B, Gassler N, Autschbach F, Ligtenberg AJM, Benner A, Holmskov U, Schirmacher P, Amerongen AVN, Rosenstiel P, Sina C, Franke A, Hafner M, Kioschis P, Schreiber S, Poustka A, Mollenhauer J (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 39
Pages Range: 833-842
Journal Issue: 3
Abstract
Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-κB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function in mucosal protection and of its broad pathogen-binding specificity. We report that DMBT1 directly interacts with dextran sulfate sodium (DSS) and carrageenan, a structurally similar sulfated polysaccharide, which is used as a texturizer and thickener in human dietary products. However, binding of DMBT1 does not reduce the cytotoxic effects of these agents to intestinal epithelial cells in vitro. DSS and carrageenan compete for DMBT1-mediated bacterial aggregation via interaction with its bacterial-recognition motif. Competition and ELISA studies identify poly-sulfated and poly-phosphorylated structures as ligands for this recognition motif, such as heparansulfate, LPS, and lipoteichoic acid. Dose-response studies in Dmbt1-/- and Dmbt1+/+ mice utilizing the DSS-induced colitis model demonstrate a differential response only to low but not to high DSS doses. We propose that DMBT1 functions as pattern-recognition molecule for poly-sulfated and polyphosphorylated ligands providing a molecular basis for its broad bacterial-binding specificity and its inhibitory effects on LPS-induced TLR4-mediated NF-κB activation. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Authors with CRIS profile
Involved external institutions
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
University of Amsterdam
Netherlands (NL)
Technische Hochschule Mittelhessen - University of Applied Sciences
Germany (DE)
University of Southern Denmark / Syddansk Universitet
Denmark (DK)
Universitätsklinikum Schleswig-Holstein (UKSH)
Germany (DE)
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
University of Amsterdam
Netherlands (NL)
Technische Hochschule Mittelhessen - University of Applied Sciences
Germany (DE)
University of Southern Denmark / Syddansk Universitet
Denmark (DK)
Universitätsklinikum Schleswig-Holstein (UKSH)
Germany (DE)
How to cite
APA:
End, C., Bikker, F., Renner, M., Bergmann, G., Lyer, S., Blaich, S.,... Mollenhauer, J. (2009). DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands. European Journal of Immunology, 39(3), 833-842. https://doi.org/10.1002/eji.200838689
MLA:
End, Caroline, et al. "DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands." European Journal of Immunology 39.3 (2009): 833-842.
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