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Cf‐02, a novel benzamide‐linked small molecule, blunts NF‐κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice
- Source :
- FASEB J
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide-linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02) (a) reduced serum levels of IgG anti-dsDNA, IL-1β, IL-6, and TNF-α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF-κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf-02 significantly inhibited secretion of IL-1β in lipopolysaccharide-stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf-02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf-02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome-driven signaling.
- Subjects :
- T cell
Interleukin-1beta
Lupus nephritis
Priming (immunology)
Biochemistry
Article
Mice
chemistry.chemical_compound
NLR Family, Pyrin Domain-Containing 3 Protein
Autophagy
Genetics
medicine
Animals
Humans
Immunologic Factors
Secretion
Benzamide
Molecular Biology
Cells, Cultured
Chemistry
Macrophages
NF-kappa B
Inflammasome
Dendritic Cells
medicine.disease
Lupus Nephritis
Small molecule
Mice, Inbred C57BL
Sjogren's Syndrome
medicine.anatomical_structure
Case-Control Studies
Cancer research
Female
Biotechnology
medicine.drug
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....5919f7a6023ae7ac935ca69ec70a9354