| http://purl.uniprot.org/citations/16319062 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16319062 | http://www.w3.org/2000/01/rdf-schema#comment | "Production of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide induced in various epithelia upon extracellular as well as intracellular bacterial challenge. Nucleotide-binding oligomerization domain protein 2 (NOD2/CARD15) is a cytosolic protein involved in intracellular recognition of microbes by sensing peptidoglycan fragments (e.g. muramyl dipeptide). We used luciferase as a reporter gene for a 2.3-kb hBD-2 promoter to test the hypothesis that NOD2 mediates the induction of hBD-2. Activation of NOD2 in NOD2-overexpressing human embryonic kidney 293 cells through its ligand muramyl dipeptide (MDP) induced hBD-2 expression. In contrast, overexpression of NOD2 containing the 3020insC frame-shift mutation, the most frequent NOD2 variant associated with Crohn disease, resulted in defective induction of hBD-2 through MDP. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for NOD2-mediated induction of hBD-2 through MDP. Moreover, the NF-kappaB inhibitor Helenalin as well as a super-repressor form of the NF-kappaB inhibitor IkappaB strongly inhibited NOD2-mediated hBD-2 promoter activation. Expression of NOD2 was detected in primary keratinocytes, and stimulation of these cells with MDP induced hBD-2 peptide release. In contrast, small interference RNA-mediated down-regulation of NOD2 expression in primary keratinocytes resulted in a defective induction of hBD-2 upon MDP treatment. Together, these data suggest that NOD2 serves as an intracellular pattern recognition receptor to enhance host defense by inducing the production of antimicrobial peptides such as hBD-2."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m511044200"xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Voss E."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Harder J."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Stange E.F."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Wehkamp J."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Schroder J.M."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/author | "Wehkamp K."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/pages | "2005-2011"xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/title | "NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2."xsd:string |
| http://purl.uniprot.org/citations/16319062 | http://purl.uniprot.org/core/volume | "281"xsd:string |
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