Abstract
We showed previously that a novel protein, transmembrane protein 126A (TMEM126A), binds to CD137 ligand (CD137L, 4-1BBL) and couples with its reverse signals in macrophages. Here, we present data showing that TMEM126A relays TLR4 signaling. Thus, up-regulation of CD54 (ICAM-1), MHC II, CD86 and CD40 expression in response to TLR4 activation was diminished in TMEM126A-deficient macrophages. Moreover in TMEM126A-deficient RAW264.7 cells, LPS/TLR4-induced late-phase JNK/SAPK and IRF-3 phosphorylation was abolished. These findings indicate that TMEM126A contributes to the TLR4 signal up-regulating the expression of genes whose products are involved in antigen presentation.
Keywords:
Antigen presenting; CD137L; Innate immunity; TMEM126A; TRL4.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation
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B7-2 Antigen / genetics
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B7-2 Antigen / immunology
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CD40 Antigens / genetics
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CD40 Antigens / immunology
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Cell Line
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Gene Expression Regulation
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / immunology
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / immunology
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Lipopolysaccharides / pharmacology
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / immunology
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology*
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Male
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Membrane Proteins / genetics*
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Membrane Proteins / immunology
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Primary Cell Culture
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Protein Binding
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Signal Transduction / immunology*
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Toll-Like Receptor 4 / genetics*
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Toll-Like Receptor 4 / immunology
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics*
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Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
Substances
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B7-2 Antigen
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CD40 Antigens
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Histocompatibility Antigens Class II
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Interferon Regulatory Factor-3
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Irf3 protein, mouse
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Lipopolysaccharides
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Membrane Proteins
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TLR4 protein, human
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TMEM126A protein, mouse
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Toll-Like Receptor 4
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Intercellular Adhesion Molecule-1
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MAP Kinase Kinase 4