Inhibiting Mer receptor tyrosine kinase suppresses STAT1, SOCS1/3, and NF-κB activation and enhances inflammatory responses in lipopolysaccharide-induced acute lung injury
Copyright policy )Inhibiting Mer receptor tyrosine kinase suppresses STAT1, SOCS1/3, and NF-κB activation and enhances inflammatory responses in lipopolysaccharide-induced acute lung injury
ABSTRACTMer 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.
- Ewha Womans University Korea (Republic of)
Lipopolysaccharides, Male, Mice, Inbred BALB C, Acute Lung Injury, NF-kappa B, Receptor Protein-Tyrosine Kinases, Suppressor of Cytokine Signaling Proteins, Enzyme Activation, Mice, STAT1 Transcription Factor, Suppressor of Cytokine Signaling 1 Protein, Gene Expression Regulation, Matrix Metalloproteinase 9, Suppressor of Cytokine Signaling 3 Protein, Proto-Oncogene Proteins, Macrophages, Alveolar, Animals, Cytokines, Inflammation Mediators, Phosphorylation
Lipopolysaccharides, Male, Mice, Inbred BALB C, Acute Lung Injury, NF-kappa B, Receptor Protein-Tyrosine Kinases, Suppressor of Cytokine Signaling Proteins, Enzyme Activation, Mice, STAT1 Transcription Factor, Suppressor of Cytokine Signaling 1 Protein, Gene Expression Regulation, Matrix Metalloproteinase 9, Suppressor of Cytokine Signaling 3 Protein, Proto-Oncogene Proteins, Macrophages, Alveolar, Animals, Cytokines, Inflammation Mediators, Phosphorylation
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