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Updated: Nov 30, 2025
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Canagliflozin alleviates LPS-induced acute lung injury by modulating alveolar macrophage polarization
Fengyu Lin1, Chao Song1, Yanjun Zeng1
1Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, 410008, China.
Background:
Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, is a novel therapeutic agent that exhibits multiple actions in type 2 diabetes. CANA can regulate intracellular glucose metabolism and exert anti-inflammatory effects in immune cells. Alveolar macrophage polarization balance is often associated with lower inflammation in acute lung injury (ALI). However, little is known about the anti-inflammatory effect of CANA on ALI.
Methods:
This study aimed to determine the effect of CANA on ALI as well as its potential ability to modulate alveolar macrophage polarization in ALI mouse models and bone marrow-derived macrophages (BMDMs).
Results:
The histopathological changes indicated that CANA alleviated lung injury in lipopolysaccharide-induced ALI mice models and exerted anti-inflammatory effects in the presence of lower levels of tumor necrosis factor-ɑ, interleukin-6, and interleukin-1β in bronchoalveolar lavage fluid (BALF) and serum. Moreover, flow cytometry analysis of mouse BALF cells and BMDMs demonstrated that CANA can modulate and reconstitute M1 and M2 macrophage balance, inhibiting macrophages with the M1 phenotype while promoting macrophages to shift to the M2 phenotype. Immunohistochemistry and reverse transcription polymerase chain reaction were also performed.
Conclusions:
These findings indicate that CANA alleviates lung injury and exerts anti-inflammatory effects by modulating alveolar macrophage polarization balance, suggesting that CANA might act as a novel anti-inflammatory drug for treating ALI.
Insights
Canagliflozin (CANA) alleviates acute lung injury (ALI) by reducing inflammation and shifting macrophage balance. This sodium-glucose cotransporter 2 inhibitor shows potential as a novel anti-inflammatory treatment for ALI.
Area of Science:
- Pharmacology
- Immunology
- Pulmonology
Background:
- Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, has known roles in type 2 diabetes, including glucose metabolism regulation and immune cell anti-inflammatory effects.
- Alveolar macrophage polarization is critical for regulating lung inflammation in acute lung injury (ALI).
- The anti-inflammatory impact of CANA on ALI remains largely unexplored.
Purpose of the Study:
- To investigate the therapeutic effect of CANA on ALI.
- To determine if CANA can modulate alveolar macrophage polarization in ALI.
Main Methods:
- Utilized lipopolysaccharide-induced ALI mouse models and bone marrow-derived macrophages (BMDMs).
- Assessed lung injury, inflammation markers (TNF-ɑ, IL-6, IL-1β) in bronchoalveolar lavage fluid (BALF) and serum.
- Employed flow cytometry, immunohistochemistry, and reverse transcription polymerase chain reaction to analyze macrophage polarization (M1/M2 balance).
Main Results:
- CANA treatment alleviated lung histopathological damage in ALI mouse models.
- CANA significantly reduced pro-inflammatory cytokines (TNF-ɑ, IL-6, IL-1β) in BALF and serum.
- CANA modulated macrophage polarization, inhibiting M1 phenotype and promoting M2 phenotype in both BALF cells and BMDMs.
Conclusions:
- Canagliflozin demonstrates efficacy in alleviating lung injury and inflammation associated with ALI.
- The anti-inflammatory effects of CANA are mediated through the modulation of alveolar macrophage polarization.
- CANA presents potential as a novel therapeutic agent for treating acute lung injury.
