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Updated: Feb 7, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
A novel DYRK1A inhibitor alleviates lipopolysaccharide-induced acute lung injury via suppressing inflammatory pathway
Xi Zeng1, Lingyu Cui2, Yetong Li3
1Department of Clinical Pharmacy, General Hospital of Northern Theater Command, Shenyang, China; Department of Pharmacy, the 78th Group Army Hospital of Chinese PLA, Mudanjiang, China.
Background:
Acute lung injury (ALI) is a highly fatal inflammatory disease, lacking of safe and effective therapeutic drugs. Anti-inflammatory treatment is an effective strategy of ALI.
Purpose:
This study aimed to identify compound 24, a novel dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) inhibitor, as an anti-inflammatory agent for ALI.
Methods:
We established the LPS-induced RAW 264.7 cell inflammation model and the mouse ALI model. ELISA and real time-PCR (RT-PCR) were used to detect the levels of inflammatory factors in supernatant and lung. Reactive oxygen species (ROS) production was measured by flow cytometry using DCFH-DA. HE was used to determine the pathological damage of lung. Immunohistochemistry was applied to detect inflammatory biomarkers in lung. The infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) was determine by flow cytometry. Molecular docking, cellular thermal shift assay (CETSA), and western blot (WB) were conducted to measure the drug-target interaction and inflammatory signaling.
Results:
Pretreatment with compound 24 significantly reduced the levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitric oxide (NO), and ROS in vitro, and alleviated the release of inflammatory factors, infiltration of inflammatory cells, and tissue damage in the lung. Mechanistic studies indicated that compound 24 might exert its anti-inflammatory effect by targeting DYRK1A and inhibiting the TLR4/NF-κB signaling pathway.
Conclusions:
In summary, compound 24 exerted anti-inflammation effect with potential value for further development into a therapeutic drug for ALI treatment.
Insights
Compound 24, a DYRK1A inhibitor, shows significant anti-inflammatory effects in acute lung injury (ALI) models. It reduces inflammatory mediators and tissue damage, offering potential for ALI therapeutic development.
Area of Science:
- Pharmacology
- Immunology
- Molecular Biology
Background:
- Acute lung injury (ALI) is a severe inflammatory condition with limited therapeutic options.
- Anti-inflammatory strategies are crucial for managing ALI.
Purpose of the Study:
- To identify compound 24, a novel DYRK1A inhibitor, as a potential anti-inflammatory agent for ALI.
- To evaluate the efficacy of compound 24 in preclinical ALI models.
Main Methods:
- Established LPS-induced RAW 264.7 cell and mouse ALI models.
- Assessed inflammatory mediators (TNF-α, IL-6, IL-1β, NO, ROS) using ELISA, RT-PCR, and flow cytometry.
- Evaluated lung pathology, inflammatory cell infiltration, and drug-target interactions via HE staining, flow cytometry, molecular docking, CETSA, and WB.
Main Results:
- Compound 24 significantly reduced inflammatory mediators (TNF-α, IL-6, IL-1β, NO, ROS) in vitro.
- Compound 24 alleviated lung inflammation, inflammatory cell infiltration, and tissue damage in vivo.
- Mechanistic studies suggested compound 24 targets DYRK1A and inhibits the TLR4/NF-κB pathway.
Conclusions:
- Compound 24 demonstrates potent anti-inflammatory effects.
- Compound 24 holds promise as a therapeutic candidate for acute lung injury.
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