HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blüml, S. Articles by Leitinger, N. Search for Related Content PubMed PubMed Citation Articles by Blüml, S. Articles by Leitinger, N. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LECITHIN

Oxidized Phospholipids Negatively Regulate Dendritic Cell Maturation Induced by TLRs and CD40¹

Stefan Blüml^*, Stefanie Kirchberger^*, Valery N. Bochkov, Gerhard Krönke^2,, Karl Stuhlmeier, Otto Majdic^*, Gerhard J. Zlabinger^*, Walter Knapp^3,*, Bernd R. Binder, Johannes Stöckl^4,* and Norbert Leitinger^2,

^* Institute of Immunology, Medical University of Vienna, Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, and Ludwig Boltzmann Institute for Rheumatology, Vienna, Austria

Maturation of dendritic cells (DCs) induced by pathogen-derived signals via TLRs is a crucial step in the initiation of an adaptive immune response and therefore has to be well controlled. In this study, we demonstrate that oxidized phospholipids (ox-PLs), which are generated during infections, apoptosis, and tissue damage, interfere with DC activation, preventing their maturation. ox-PLs blocked TLR-3- and TLR-4-mediated induction of the costimulatory molecules CD40, CD80, CD83, and CD86, the cytokines IL-12 and TNF, as well as lymphocyte stimulatory capacity. CD40 and TLR-2-mediated cytokine production was also inhibited, whereas up-regulation of costimulatory molecules via these receptors was not affected by ox-PLs. Thus, formation of ox-PLs during the course of an inflammatory response may represent a negative-feedback loop preventing excessive and sustained immune reactions through regulating DC maturation.

This article has been cited by other articles:

				K. L.L. Habets, G. H.M. van Puijvelde, L. M. van Duivenvoorde, E. J.A. van Wanrooij, P. de Vos, J.-W. Cohen Tervaert, T. J.C. van Berkel, R. E.M. Toes, and J. Kuiper Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice Cardiovasc Res, November 12, 2009; (2009) cvp338v2. [Abstract] [Full Text] [PDF]

				C. Schrauf, S. Kirchberger, O. Majdic, M. Seyerl, G.-J. Zlabinger, K. M. Stuhlmeier, M. Sachet, J. Seipelt, and J. Stockl The ssRNA Genome of Human Rhinovirus Induces a Type I IFN Response but Fails to Induce Maturation in Human Monocyte-Derived Dendritic Cells J. Immunol., October 1, 2009; 183(7): 4440 - 4448. [Abstract] [Full Text] [PDF]

				P. A. Singleton, S. Chatchavalvanich, P. Fu, J. Xing, A. A. Birukova, J. A. Fortune, A. M. Klibanov, J. G. N. Garcia, and K. G. Birukov Akt-Mediated Transactivation of the S1P1 Receptor in Caveolin-Enriched Microdomains Regulates Endothelial Barrier Enhancement by Oxidized Phospholipids Circ. Res., April 24, 2009; 104(8): 978 - 986. [Abstract] [Full Text] [PDF]

				J. A. Berliner, N. Leitinger, and S. Tsimikas The role of oxidized phospholipids in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S207 - S212. [Abstract] [Full Text] [PDF]

				A. A. Birukova, E. Alekseeva, I. Cokic, C. E. Turner, and K. G. Birukov Cross talk between paxillin and Rac is critical for mediation of barrier-protective effects by oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L593 - L602. [Abstract] [Full Text] [PDF]

				S. Bluml, B. Rosc, A. Lorincz, M. Seyerl, S. Kirchberger, O. Oskolkova, V. N. Bochkov, O. Majdic, E. Ligeti, and J. Stockl The Oxidation State of Phospholipids Controls the Oxidative Burst in Neutrophil Granulocytes J. Immunol., September 15, 2008; 181(6): 4347 - 4353. [Abstract] [Full Text] [PDF]

				C. Erridge, S. Kennedy, C. M. Spickett, and D. J. Webb Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4: ROLES FOR CD14, LPS-BINDING PROTEIN, AND MD2 AS TARGETS FOR SPECIFICITY OF INHIBITION J. Biol. Chem., September 5, 2008; 283(36): 24748 - 24759. [Abstract] [Full Text] [PDF]

				F. Gruber, O. Oskolkova, A. Leitner, M. Mildner, V. Mlitz, B. Lengauer, A. Kadl, P. Mrass, G. Kronke, B. R. Binder, et al. Photooxidation Generates Biologically Active Phospholipids That Induce Heme Oxygenase-1 in Skin Cells J. Biol. Chem., June 8, 2007; 282(23): 16934 - 16941. [Abstract] [Full Text] [PDF]

				A. T. Shamshiev, F. Ampenberger, B. Ernst, L. Rohrer, B. J. Marsland, and M. Kopf Dyslipidemia inhibits Toll-like receptor-induced activation of CD8{alpha}-negative dendritic cells and protective Th1 type immunity J. Exp. Med., February 19, 2007; 204(2): 441 - 452. [Abstract] [Full Text] [PDF]

				M. Thurnher Lipids in dendritic cell biology: messengers, effectors, and antigens J. Leukoc. Biol., January 1, 2007; 81(1): 154 - 160. [Abstract] [Full Text] [PDF]

				M. Groeneweg, E. Kanters, M. N. Vergouwe, H. Duerink, G. Kraal, M. H. Hofker, and M. P. J. de Winther Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL J. Lipid Res., October 1, 2006; 47(10): 2259 - 2267. [Abstract] [Full Text] [PDF]