The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors
Open accessAbstract
Activation of the NLRP3 inflammasome enables monocytes and macrophages to release high levels of interleukin-1β during inflammatory responses. Concentrations of extracellular calcium can increase at sites of infection, inflammation or cell activation. Here we show that increased extracellular calcium activates the NLRP3 inflammasome via stimulation of G protein-coupled calcium sensing receptors. Activation is mediated by signalling through the calcium-sensing receptor and GPRC6A via the phosphatidyl inositol/Ca2+ pathway. The resulting increase in the intracellular calcium concentration triggers inflammasome assembly and Caspase-1 activation. We identified necrotic cells as one source for excess extracellular calcium triggering this activation. In vivo, increased calcium concentrations can amplify the inflammatory response in the mouse model of carrageenan-induced footpad swelling, and this effect was inhibited in GPRC6A−/− mice. Our results demonstrate that G-protein-coupled receptors can activate the inflammasome, and indicate that increased extracellular calcium has a role as a danger signal and amplifier of inflammation. Levels of extracellular calcium can increase at sites of infection and inflammation; however, the physiological significance of this has been unclear. This work shows that extracellular calcium acts as a danger signal, triggering the NLRP3 inflammasome via two G protein-coupled receptors.
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Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
Interleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798
Masters, S. L., Dunne, A., Subramanian, S. L., Hull, R. L., Tannahill, G. M., Sharp, F. A., Becker, C., Franchi, L., Yoshihara, E., Chen, Z., et al. (2010) · Nature Immunology · doi:10.1038/ni.1935 · Cited by 1,330
Cited by
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672
Initiation and perpetuation of NLRP 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821
Mechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736
Metadata
- Authors
- Rossol, M., Pierer, M., Raulien, N., Quandt, D., Meusch, U., Rothe, K., Schubert, K., Schöneberg, T., Schaefer, M., Krügel, U., Smajilovic, S., Bräuner-Osborne, H., Baerwald, C., & Wagner, U.
- Venue
- Nature Communications
- Published
- 2012-12-27
- Volume
- 3
- Issue
- 1
- Pages
- 1329-1329
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2071517838
- Cited by
- 491
- References
- 5
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rossol, M., Pierer, M., Raulien, N., Quandt, D., Meusch, U., Rothe, K., Schubert, K., Schöneberg, T., Schaefer, M., Krügel, U., Smajilovic, S., Bräuner-Osborne, H., Baerwald, C., & Wagner, U. (2012). Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nature Communications. https://doi.org/10.1038/ncomms2339
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
