The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
NOD2/CARD15 Mediates Induction of the Antimicrobial Peptide Human Beta-defensin-2
Open accessAbstract
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.
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Citations
Cites
Antimicrobial peptides of multicellular organisms
Zasloff, M. (2002) · Nature · doi:10.1038/415389a · Cited by 8,457
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot, J.-P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J.-P., Belaiche, J., Almer, S., Tysk, C., O'Morain, C. A., Gassull, M., et al. (2001) · Nature · doi:10.1038/35079107 · Cited by 5,591
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., et al. (2001) · Nature · doi:10.1038/35079114 · Cited by 5,030
Plant pathogens and integrated defence responses to infection
Dangl, J. L., & Jones, J. D. G. (2001) · Nature · doi:10.1038/35081161 · Cited by 3,949
Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection
Girardin, S. E., Boneca, I. G., Viala, J., Chamaillard, M., Labigne, A., Thomas, G., Philpott, D. J., & Sansonetti, P. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200651200 · Cited by 2,408
Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis
Ong, P. Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., Gallo, R. L., & Leung, D. Y. M. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021481 · Cited by 1,960
β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6
Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schröder, J. M., Wang, J. M., Howard, O. M. Z., et al. (1999) · Science · doi:10.1126/science.286.5439.525 · Cited by 1,809
Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract
Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., Nuñez, G., & Flavell, R. A. (2005) · Science · doi:10.1126/science.1104911 · Cited by 1,776
Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2
Inohara, N., Ogura, Y., Fontalba, A., Gutierrez, O., Pons, F., Crespo, J., Fukase, K., Inamura, S., Kusumoto, S., Hashimoto, M., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200673200 · Cited by 1,696
A peptide antibiotic from human skin
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Self-citation
Cited by
Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
Bouskra, D., Brézillon, C., Bérard, M., Werts, C., Varona, R., Boneca, I. G., & Eberl, G. (2008) · Nature · doi:10.1038/nature07450 · Cited by 1,107
NOD-Like Receptors: Role in Innate Immunity and Inflammatory Disease
Chen, G., Shaw, M. H., Kim, Y.-G., & Nuñez, G. (2009) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092239 · Cited by 772
Intestinal barrier dysfunction in inflammatory bowel diseases
McGuckin, M. A., Eri, R., Simms, L. A., Florin, T. H. J., & Radford-Smith, G. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20539 · Cited by 627
A critical role of RICK/RIP2 polyubiquitination in Nod‐induced NF‐κB activation
Hasegawa, M., Fujimoto, Y., Lucas, P. C., Nakano, H., Fukase, K., Núñez, G., & Inohara, N. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601962 · Cited by 522
De Palma, G., Lynch, M. D. J., Lu, J., Dang, V. T., Deng, Y., Jury, J., Umeh, G., Miranda, P. M., Pigrau Pastor, M., Sidani, S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6397 · Cited by 505
Metadata
- Authors
- Voss, E., Wehkamp, J., Wehkamp, K., Stange, E. F., Schröder, J. M., & Harder, J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 281
- Issue
- 4
- Pages
- 2005-2011
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2042675697
- Cited by
- 344
- References
- 63
- FWCI
- 19.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Voss, E., Wehkamp, J., Wehkamp, K., Stange, E. F., Schröder, J. M., & Harder, J. (2006). NOD2/CARD15 Mediates Induction of the Antimicrobial Peptide Human Beta-defensin-2. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m511044200
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