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Updated: Jul 13, 2025
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
ACT001 alleviates inflammation and pyroptosis through the PPAR-γ/NF-κB signaling pathway in LPS-induced alveolar
Qiang Fu1, Na Shen2, Tao Fang2
1Department of Intensive Care Unit, Tianjin 4th Central Hospital, No.1 Zhongshan Road, Tianjin, 300140, China. act001fq@sohu.com.
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.
Insights
ACT001 reduces inflammation and pyroptosis in acute lung injury models. It works by activating PPAR-γ and inhibiting the NF-κB pathway in macrophages.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- ACT001 is an anti-inflammatory agent with known roles in tumors, intracranial, and fibrotic diseases.
- Its impact on acute lung injury (ALI) remains largely unexplored.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-pyroptotic effects of ACT001.
- To elucidate the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced alveolar macrophages.
Main Methods:
- Utilized NR8383 alveolar macrophages stimulated with LPS to model ALI.
- Assessed inflammatory cytokine levels, pyroptosis rates, and inflammasome protein expression.
- Investigated the role of the PPAR-γ/NF-κB signaling pathway, using a PPAR-γ inhibitor for validation.
Main Results:
- ACT001 significantly decreased inflammatory factor release and cell pyroptosis.
- Downregulated key pyroptosis markers including NLRP3, ASC, caspase-1 p20, and GSDMD-N.
- Demonstrated that ACT001 activates PPAR-γ, subsequently inhibiting the NF-κB pathway, with effects reversed by a PPAR-γ inhibitor.
Conclusions:
- ACT001 effectively ameliorates inflammation and pyroptosis in LPS-induced macrophages.
- The mechanism involves the PPAR-γ/NF-κB signaling pathway.
- Highlights ACT001's therapeutic potential for acute lung injury.
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