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Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.

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.

SUBMITTER: von Kampen O

PROVIDER: S-EPMC2888403 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.

von Kampen Oliver O Lipinski Simone S Till Andreas A Martin Seamus J SJ Nietfeld Wilfried W Lehrach Hans H Schreiber Stefan S Rosenstiel Philip P

The Journal of biological chemistry 20100412 26

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 intra ...[more]

PMID: 20385562

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