Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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CD40 Antigens / metabolism*
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CD40 Ligand / pharmacology
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Cell Differentiation
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Cytokines / biosynthesis
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DNA, Complementary / genetics
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Dendritic Cells / cytology*
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Feedback
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Humans
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In Vitro Techniques
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Inflammation / immunology
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Inflammation / metabolism
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / drug effects
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Membrane Glycoproteins / metabolism*
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NF-kappa B / metabolism
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Oxidation-Reduction
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Peptidoglycan / pharmacology
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Phosphatidylcholines / pharmacology
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Phospholipids / chemistry
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Phospholipids / immunology*
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Phospholipids / metabolism*
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Poly I-C / pharmacology
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Receptors, Cell Surface / metabolism*
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Signal Transduction / drug effects
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
Substances
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CD40 Antigens
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Cytokines
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DNA, Complementary
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Lipopolysaccharides
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Membrane Glycoproteins
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NF-kappa B
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Peptidoglycan
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Phosphatidylcholines
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Phospholipids
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Receptors, Cell Surface
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TLR2 protein, human
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TLR3 protein, human
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TLR4 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
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oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
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CD40 Ligand
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Poly I-C