AI Article Synopsis
- * Researchers used mouse-derived macrophages and THP-1 cells to assess CDDO-Me's effects on various inflammasome activators and measured key inflammatory markers.
- * Results showed that CDDO-Me effectively reduced the activation of the NLRP3 inflammasome in lab tests and significantly decreased inflammation and liver damage in mouse models of ALI, indicating its potential therapeutic role.
Article Abstract
Objective: To investigate the inhibitory effect of bardoxolone methyl (CDDO-Me) on activation of NLRP3 inflammasome and its mechanism for alleviating acute liver injury (ALI).
Methods: Mouse bone marrow-derived macrophages (BMDM) and THP-1 cells were pre-treated with CDDO-Me followed by treatment with Nigericin, ATP, MSU, intracellular LPS transfection for activation of NLRP3 inflammasomes, or poly A: T for activation of AIM2 inflammasomes. The levels of caspase-1 and IL-1β in the cell culture supernatant was determined with Western blotting and ELISA to assess the inhibitory effect of CDDO-Me on NLRP3 inflammasomes and its specificity. In the animal experiment, male C57BL/6J mouse models of acetaminophen-induced ALI were treated with low-dose (20 mg/kg) and high-dose (40 mg/kg) CDDO-Me, and the changes in serum levels of IL-1β, TNF- , AST and ALT were measured by ELISA and liver tissue pathology was observed using HE staining.
Results: In mouse BMDM and THP-1 cells, CDDO-Me dose-dependently inhibited the activation of NLRP3 inflammasomes without significantly affecting the secretion of non-inflammasome-related inflammatory factors IL-6 and TNF- or AIM2 inflammasome activation. In the mouse models of ALI, CDDO-Me treatment at both the low and high doses significantly reduced serum levels of IL-1β, AST and ALT, ameliorated histological changes and reduced inflammatory cell infiltration in the liver tissue, and the effects exhibited a distinct dose dependence.
Conclusion: CDDO-Me can specifically inhibit the activation of NLRP3 inflammasomes to alleviate acetaminophen-induced ALI in mice.
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| http://dx.doi.org/10.12122/j.issn.1673-4254.2024.09.05 | DOI Listing |
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