Abstract
Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the present study was to examine the role of Mer signaling in the down-regulation of TLR4 activation-driven immune responses in mice, i.t.-treated with LPS, using the specific Mer-blocking antibody. At 4 h and 24 h after LPS treatment, expression of Mer protein in alveolar macrophages and lung tissue decreased, sMer in BALF increased significantly, and Mer activation increased. Pretreatment with anti-Mer antibody did not influence the protein levels of Mer and sMer levels. Anti-Mer antibody significantly reduced LPS-induced Mer activation, phosphorylation of Akt and FAK, STAT1 activation, and expression of SOCS1 and -3. Anti-Mer antibody enhanced LPS-induced inflammatory responses, including activation of the NF-κB pathway; the production of TNF-α, IL-1β, and MIP-2 and MMP-9 activity; and accumulation of inflammatory cells and the total protein levels in BALF. These results indicate that Mer plays as an intrinsic feedback inhibitor of the TLR4- and inflammatory mediator-driven immune responses during acute lung injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Lung Injury / chemically induced*
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Acute Lung Injury / genetics
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Acute Lung Injury / immunology
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Animals
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Cytokines / genetics
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Cytokines / immunology
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Enzyme Activation / drug effects
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Inflammation Mediators / immunology
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Lipopolysaccharides / toxicity*
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Macrophages, Alveolar / immunology*
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Macrophages, Alveolar / pathology
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Male
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / immunology
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Mice
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Mice, Inbred BALB C
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NF-kappa B / genetics
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NF-kappa B / immunology*
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Phosphorylation / drug effects
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Phosphorylation / genetics
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Phosphorylation / immunology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / immunology*
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / immunology*
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / immunology*
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Toll-Like Receptor 4 / agonists
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
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c-Mer Tyrosine Kinase
Substances
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Cytokines
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Inflammation Mediators
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Lipopolysaccharides
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NF-kappa B
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Proto-Oncogene Proteins
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STAT1 Transcription Factor
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Socs1 protein, mouse
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Socs3 protein, mouse
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Stat1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Mertk protein, mouse
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Receptor Protein-Tyrosine Kinases
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c-Mer Tyrosine Kinase
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Matrix Metalloproteinase 9
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Mmp9 protein, mouse