Abstract
CARD-containing MAGUK protein 1 (CARMA1) plays a crucial role in regulating adaptive immune responses upon T-cell receptor (TCR) activation in T cells. Its role in regulating host mucosal innate immune response such as upregulation of mucin remains unknown. Here we show that CARMA1 acts as a key signaling mediator for synergistic upregulation of MUC5AC mucin by bacterium nontypeable Haemophilus influenzae (NTHi) and phorbol ester PMA in respiratory epithelial cells. NTHi-induced TLR-dependent TRAF6-MKK3-p38 MAPK signaling pathway synergizes with PKCθ-MEK-ERK signaling pathway. CARMA1 plays a crucial role in mediating this synergistic effect via TRAF6, thereby resulting in synergistic upregulation of MUC5AC mucin. Thus our study unveils a novel role for CARMA1 in mediating host mucosal innate immune response.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CARD Signaling Adaptor Proteins / metabolism*
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Cell Line
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Epithelial Cells / drug effects
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Epithelial Cells / enzymology
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Epithelial Cells / microbiology
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Guanylate Cyclase / metabolism*
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Haemophilus influenzae / drug effects
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Haemophilus influenzae / physiology
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Humans
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Isoenzymes / metabolism*
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MAP Kinase Kinase 3 / metabolism
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MAP Kinase Kinase 6 / metabolism
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MAP Kinase Signaling System / drug effects
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Membrane Proteins / metabolism*
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Mice
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Mucin 5AC / metabolism*
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Protein Kinase C / metabolism*
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Protein Kinase C-theta
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Signal Transduction* / drug effects
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TNF Receptor-Associated Factor 6 / metabolism*
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Tetradecanoylphorbol Acetate / pharmacology
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Toll-Like Receptor 2 / metabolism*
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Up-Regulation* / drug effects
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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CARD Signaling Adaptor Proteins
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Isoenzymes
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Membrane Proteins
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Mucin 5AC
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TNF Receptor-Associated Factor 6
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Toll-Like Receptor 2
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PRKCQ protein, human
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Protein Kinase C
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Protein Kinase C-theta
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 3
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MAP Kinase Kinase 6
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CARD11 protein, human
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Guanylate Cyclase
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Tetradecanoylphorbol Acetate