Abstract
Background
ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known.
Objective
The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages.
Methods
NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor.
Results
Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed.
Conclusion
ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages.
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Funding
This work was supported by grants from Science and Technology planning project of Tianjin (20JCYBJC01000), Science and Technology Project of Tianjin Municipal Health Commission (ZC20026, TJWJ2021QN055, TJWJ2022QN049), Integrated Traditional Chinese and Western Medicine project of Tianjin Municipal Health Commission (2021190).
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Fu, Q., Shen, N., Fang, T. et al. ACT001 alleviates inflammation and pyroptosis through the PPAR-γ/NF-κB signaling pathway in LPS-induced alveolar macrophages. Genes Genom 46, 323–332 (2024). https://doi.org/10.1007/s13258-023-01455-w
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DOI: https://doi.org/10.1007/s13258-023-01455-w