Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization
IntroductionMycobacterium abscessus (M. abscessus) is a highly drug-resistant pathogen responsible for chronic pulmonary inflammation in humans. The cardiac glycoside ouabain exhibits broad anti-inflammatory effects in various disease models, but its therapeutic potential against M. abscessus-induce...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633882/full |
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| Summary: | IntroductionMycobacterium abscessus (M. abscessus) is a highly drug-resistant pathogen responsible for chronic pulmonary inflammation in humans. The cardiac glycoside ouabain exhibits broad anti-inflammatory effects in various disease models, but its therapeutic potential against M. abscessus-induced pneumonia remains unexplored.MethodsWe investigated the role of ouabain in M. abscessus-induced inflammation using in vivo and in vitro models. Inflammatory responses were assessed through cytokine expression analysis (TNF-α, IL-6, IL-1β), histopathological examination (H&E staining), transcriptomic profiling, IHC, TEM and qPCR. The effects of ouabain on NLRP3 inflammasome activation and macrophage polarization were also evaluated.ResultsOuabain significantly reduced M. abscessus-induced inflammation by suppressing proinflammatory cytokines (TNF-α, IL-6, IL-1β) and attenuating lung tissue damage. Transcriptomic and qPCR analyses confirmed that ouabain downregulated NLRP3 inflammasome activity and IL-1β secretion in vivo. In vitro studies further demonstrated that ouabain inhibited NLRP3 inflammasome activation and M1 macrophage polarization.DiscussionThese findings indicate that ouabain mitigates M. abscessus-induced pulmonary inflammation through dual mechanisms: suppression of NLRP3 inflammasome activation and modulation of M1 macrophage polarization. This study highlights ouabain’s potential as a therapeutic candidate for M. abscessus infections. |
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| ISSN: | 1664-3224 |