Abstract
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified molecule involved in the amplification of inflammation. To determine the regulation of TREM-1, we studied TREM-1 expression and soluble TREM-1 plasma levels upon i.v. LPS challenge in healthy humans in vivo and in vitro. Granulocyte TREM-1 expression was high at baseline and immediately down-regulated upon LPS exposure along with an increase in soluble TREM-1. Monocytes displayed a gradual up-regulation of TREM-1 upon LPS in vivo and in vitro. In vitro studies extended these findings to highly purified lipoteichoic acid and Streptococcus pneumoniae. Nonbacterial TLR ligands such as polyinosine-polycytidylic acid and imidazoquinoline, as well as the TLR9 ligand CpG, did not impact TREM-1 expression. The LPS-induced alterations in TREM-1 surface expression were not a result of increased TNF-alpha or IL-10. Inhibitor studies disclosed a PI3K-dependent pathway in LPS-induced up-regulation of TREM-1 on monocytes, whereas MAPK played a limited role.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Separation
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Down-Regulation / immunology
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Endotoxemia / blood
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Endotoxemia / enzymology
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Endotoxemia / immunology*
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Granulocytes / immunology
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Granulocytes / metabolism
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Humans
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Injections, Intravenous
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Lipopolysaccharides / administration & dosage
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Lipopolysaccharides / pharmacology
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Male
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / blood
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Monocytes / enzymology
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Monocytes / immunology
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Monocytes / metabolism
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Phosphatidylinositol 3-Kinases / physiology
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / biosynthesis*
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Receptors, Immunologic / blood
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Solubility
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Triggering Receptor Expressed on Myeloid Cells-1
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / physiology
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Up-Regulation / immunology
Substances
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, Immunologic
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TREM1 protein, human
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Triggering Receptor Expressed on Myeloid Cells-1
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Tumor Necrosis Factor-alpha
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Phosphatidylinositol 3-Kinases