The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice
Open accessAbstract
MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1β, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1β release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.
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Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
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Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
Blevins, H. M., Xu, Y., Biby, S., & Zhang, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.879021 · Cited by 587
The NLRP3 inflammasome: Mechanism of action, role in disease and therapies
Wang, L., & Hauenstein, A. V. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100889 · Cited by 426
The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes
Sallman, D. A., & List, A. (2019) · Blood · doi:10.1182/blood-2018-10-844654 · Cited by 273
Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome
Li, H., Guan, Y., Liang, B., Ding, P., Hou, X., Wei, W., & Ma, Y. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175091 · Cited by 258
Ambrus-Aikelin, G., Takeda, K., Joetham, A., Lazic, M., Povero, D., Santini, A. M., Pranadinata, R., Johnson, C. D., McGeough, M. D., Beasley, F. C., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-39805-z · Cited by 28
Metadata
- Authors
- Perera, A. P., Fernando, R., Shinde, T., Gundamaraju, R., Southam, B., Sohal, S. S., Robertson, A. A. B., Schroder, K., Kunde, D., & Eri, R.
- Venue
- Scientific Reports
- Published
- 2018-06-05
- Volume
- 8
- Issue
- 1
- Pages
- 8618-8618
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2806590169
- Cited by
- 295
- References
- 12
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- gold
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