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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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633882/full |
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| author | Nan Li Nan Li Nan Li Songqiang Huang Songqiang Huang Xing Shi Kuo Lu Kuo Lu Xiu Yu Chen Qiu Rongchang Chen |
| author_facet | Nan Li Nan Li Nan Li Songqiang Huang Songqiang Huang Xing Shi Kuo Lu Kuo Lu Xiu Yu Chen Qiu Rongchang Chen |
| author_sort | Nan Li |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-a63c302fcf6c440cbff4016ddfaaf49f2025-08-20T03:36:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16338821633882Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarizationNan Li0Nan Li1Nan Li2Songqiang Huang3Songqiang Huang4Xing Shi5Kuo Lu6Kuo Lu7Xiu Yu8Chen Qiu9Rongchang Chen10The Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaCollege of Food Science and Pharmaceutical Engineering, Zaozhuang University, Zaozhuang, Shandong, ChinaDepartment of Pharmacology, Joint Laboratory of Guangdong–Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaDepartment of Pharmacology, Joint Laboratory of Guangdong–Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaHenan International Joint Laboratory of Children’s Infectious Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaThe Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People’s Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaIntroductionMycobacterium 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633882/fullMycobacterium abscessusouabainpulmonary inflammationM1 macrophage polarizationNLRP3 inflammasome activation |
| spellingShingle | Nan Li Nan Li Nan Li Songqiang Huang Songqiang Huang Xing Shi Kuo Lu Kuo Lu Xiu Yu Chen Qiu Rongchang Chen Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization Frontiers in Immunology Mycobacterium abscessus ouabain pulmonary inflammation M1 macrophage polarization NLRP3 inflammasome activation |
| title | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization |
| title_full | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization |
| title_fullStr | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization |
| title_full_unstemmed | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization |
| title_short | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization |
| title_sort | ouabain alleviates mycobacterium abscessus triggered inflammatory responses through dual regulation of nlrp3 inflammasome activity and m1 macrophage polarization |
| topic | Mycobacterium abscessus ouabain pulmonary inflammation M1 macrophage polarization NLRP3 inflammasome activation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633882/full |
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