The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome
Open accessAbstract
Background: The proinflammatory cytokines interleukin 1β (IL-1β) and IL-18 are central players in the pathogenesis of inflammatory bowel disease (IBD). In response to a variety of microbial components and crystalline substances, both cytokines are processed via the caspase-1-activating multiprotein complex, the NLRP3 inflammasome. Here, the role of the NLRP3 inflammasome in experimental colitis induced by dextran sodium sulfate (DSS) was examined. Methods: IL-1β production in response to DSS was studied in macrophages of wild-type, caspase-1 −/− , NLRP3 −/− , ASC −/− , cathepsin B −/− or cathepsin L −/− mice. Colitis was induced in C57BL/6 and NLRP3 −/− mice by oral DSS administration. A clinical disease activity score was evaluated daily. Histological colitis severity and expression of cytokines were determined in colonic tissue. Results: Macrophages incubated with DSS in vitro secreted high levels of IL-1β in a caspase-1-dependent manner. IL-1β secretion was abrogated in macrophages lacking NLRP3, ASC or caspase-1, indicating that DSS activates caspase-1 via the NLRP3 inflammasome. Moreover, IL-1β secretion was dependent on phagocytosis, lysosomal maturation, cathepsin B and L, and reactive oxygen species (ROS). After oral administration of DSS, NLRP3 −/− mice developed a less severe colitis than wild-type mice and produced lower levels of proinflammatory cytokines in colonic tissue. Pharmacological inhibition of caspase-1 with pralnacasan achieved a level of mucosal protection comparable with NLRP3 deficiency. Conclusions: The NLRP3 inflammasome was identified as a critical mechanism of intestinal inflammation in the DSS colitis model. The NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for patients with IBD.
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Cites
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Self-citationCryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
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Self-citationInnate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658
Self-citationThe Inflammasomes: Guardians of the Body
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Self-citationActivation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
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Targeting the NLRP3 inflammasome in inflammatory diseases
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Metadata
- Authors
- Bauer, C., Duewell, P., Mayer, C., Lehr, H. A., Fitzgerald, K. A., Dauer, M., Tschopp, J., Endres, S., Latz, E., & Schnurr, M.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2010-05-04
- Volume
- 59
- Issue
- 9
- Pages
- 1192-1199
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2166209782
- Cited by
- 906
- References
- 11
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- green
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- Bauer, C., Duewell, P., Mayer, C., Lehr, H. A., Fitzgerald, K. A., Dauer, M., Tschopp, J., Endres, S., Latz, E., & Schnurr, M. (2010). Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut. https://doi.org/10.1136/gut.2009.197822
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