Abstract
Caspase activating and recruitment domain 8 (CARD8) has been implicated as a co-regulator of several pro-inflammatory and apoptotic signaling pathways. In the present study, we demonstrate a specific modulation of NOD2-induced signaling by CARD8 in intestinal epithelial cells. We show that CARD8 physically interacts with NOD2 and inhibits nodosome assembly and subsequent signaling upon muramyl-dipeptide stimulation. Furthermore, CARD8 inhibits the direct bactericidal effect of NOD2 against intracellular infection by Listeria monocytogenes. Thus, CARD8 represents a novel molecular switch involved in the endogenous regulation of NOD2-dependent inflammatory processes in epithelial cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
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Anti-Bacterial Agents / pharmacology
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Blotting, Western
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CARD Signaling Adaptor Proteins / genetics
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CARD Signaling Adaptor Proteins / metabolism*
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Caco-2 Cells
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Cell Line
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Cell Line, Tumor
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Colon / enzymology*
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Crohn Disease / genetics
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Crohn Disease / metabolism
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Crohn Disease / pathology
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Gene Expression Profiling
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Gentamicins / pharmacology
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HT29 Cells
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HeLa Cells
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Humans
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Intracellular Space / drug effects
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Intracellular Space / metabolism
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Intracellular Space / microbiology
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Listeria monocytogenes / growth & development
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Male
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Microscopy, Fluorescence
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nod2 Signaling Adaptor Protein / genetics
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Nod2 Signaling Adaptor Protein / metabolism*
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Protein Binding
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Transfection
Substances
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Anti-Bacterial Agents
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CARD Signaling Adaptor Proteins
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CARD8 protein, human
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Gentamicins
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Luminescent Proteins
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NOD2 protein, human
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Neoplasm Proteins
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Nod2 Signaling Adaptor Protein
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Acetylmuramyl-Alanyl-Isoglutamine