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Updated: Nov 3, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Exosomes derived from LPS-induced MHs cells prompted an inflammatory response in sepsis-induced acute lung injury
Xintong Sui1, Wei Liu1, Zhi Liu1
1Emergency Department, First Hospital of China Medical University, Shenyang City, 110001, Liaoning Province, China.
Abstract:
Exosome is a novel tool with an essential role in cell communication. However, its role in the pathogenesis of sepsis-induced acute lung injury is currently unknown. Here, we first found that lipopolysaccharide (LPS) could up-regulate the expression of pro-inflammatory cytokines and promote exosomes release in the murine alveolar macrophage cell line (MHs cells). Moreover, we found MHs cells derived exosomes also maintain the pro-inflammatory effect after LPS stimulation. Treating with hydrochloride hydrate (GW4869) could dose-dependently downregulated the release of exosomes and inhibited the upregulation of inflammatory cytokines in MHs cells with LPS treatment. Also, we further identified GW4869 administration induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines in lung tissue, and inhibit serum exosomes release. These results indicate that the downregulation of exosome release by GW4869 might protect lung tissue from LPS induced injury through the suppression of excessive inflammatory responses, suggesting its potential therapeutic effects on sepsis-induced acute lung injury.
Insights
Lipopolysaccharide (LPS) triggers inflammation and exosome release in lung cells. Inhibiting exosome release with GW4869 protected against LPS-induced lung injury, suggesting therapeutic potential for sepsis.
Area of Science:
- Cell Biology
- Immunology
- Pathology
Background:
- Exosomes are key mediators of intercellular communication.
- The role of exosomes in sepsis-induced acute lung injury (ALI) remains unclear.
- Lipopolysaccharide (LPS) is a potent trigger of inflammatory responses in ALI.
Purpose of the Study:
- To investigate the role of exosomes in LPS-induced ALI.
- To evaluate the therapeutic potential of inhibiting exosome release in sepsis-induced ALI.
Main Methods:
- Utilized murine alveolar macrophage cell line (MHs cells) stimulated with LPS.
- Administered GW4869, an exosome release inhibitor, to assess its effects.
- Analyzed pro-inflammatory cytokine expression, exosome release, and lung histopathology.
- Measured serum exosome levels in vivo.
Main Results:
- LPS upregulated pro-inflammatory cytokines and exosome release in MHs cells.
- MHs cell-derived exosomes retained pro-inflammatory effects post-LPS stimulation.
- GW4869 dose-dependently inhibited exosome release and inflammatory cytokine upregulation.
- GW4869 treatment reduced lung histopathology, inflammatory cytokines, and serum exosome release.
Conclusions:
- Exosome release contributes to LPS-induced ALI pathogenesis.
- Inhibiting exosome release via GW4869 demonstrates protective effects against ALI.
- Targeting exosome release presents a potential therapeutic strategy for sepsis-induced ALI.
