The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
Open accessAbstract
Inflammasomes activate caspase-1 for processing and secretion of the cytokines interleukin-1beta (IL-1beta) and IL-18. Cryopyrin/NALP3/NLRP3 is an essential component of inflammasomes triggered by microbial ligands, danger-associated molecular patterns (DAMPs), and crystals. Inappropriate Cryopyrin activity has been incriminated in the pathogenesis of gouty arthritis, Alzheimer's, and silicosis. Therefore, inhibitors of the Nalp3 inflammasome offer considerable therapeutic promise. In this study, we show that the type 2 diabetes drug glyburide prevented activation of the Cryopyrin inflammasome. Glyburide's cyclohexylurea group, which binds to adenosine triphosphatase (ATP)-sensitive K(+) (K(ATP)) channels for insulin secretion, is dispensable for inflammasome inhibition. Macrophages lacking K(ATP) subunits or ATP-binding cassette transporters also activate the Cryopyrin inflammasome normally. Glyburide analogues inhibit ATP- but not hypothermia-induced IL-1beta secretion from human monocytes expressing familial cold-associated autoinflammatory syndrome-associated Cryopyrin mutations, thus suggesting that inhibition occurs upstream of Cryopyrin. Concurrent with the role of Cryopyrin in endotoxemia, glyburide significantly delays lipopolysaccharide-induced lethality in mice. Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1beta secretion.
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“Glyburide is a commonly used sulfonylurea drug for the treatment of type 2 diabetes and was recently shown to inhibit the NLRP-3 inflammasome through a mechanism that appears to be different from that involved in its ability to promote insulin secretion from pancreatic β-cells (38).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [38]
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Metadata
- Authors
- Lamkanfi, M., Mueller, J. L., Vitari, A. C., Misaghi, S., Fedorova, A., Deshayes, K., Lee, W. P., Hoffman, H. M., & Dixit, V. M.
- Affiliations
- Genentech (US)
- University of California San Diego (US)
- Corresponding author
- Dixit, Vishva M.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-10-05
- Volume
- 187
- Issue
- 1
- Pages
- 61-70
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2762099
- OpenAlex
- W2134007048
- Cited by
- 820
- References
- 35
- Citations by year
- 2026: 25 · 2025: 44 · 2024: 63 · 2023: 50 · 2022: 67 · 2021: 52 · 2020: 66 · 2019: 64 · 2018: 62 · 2017: 47 · 2016: 42 · 2015: 68 · 2014: 47 · 2013: 44 · 2012: 31
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI052430)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- glibenclamide, NLRP3 inflammasome, NLRP3, caspase-1, IL-1β, IL-18, ATP-sensitive potassium channels, ABC transporters, monocytes, lipopolysaccharide, endotoxemia, gout, type 2 diabetes drugs, inflammasome inhibitors
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adenosine Triphosphatases, Adenosine Triphosphate, Animals, Carrier Proteins, Cells, Cultured, Enzyme Activation, Glyburide, Humans, Hypoglycemic Agents, Inflammation, Lipopolysaccharides, Macrophages, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, Mutation, Random Allocation, Salmonella typhimurium, Mice, Knockout, Caspase 1, Interleukin-18, Mice, Interleukin-1beta
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