Dynasore Alleviates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis

Area of Science:

• Immunology
• Cell Biology
• Respiratory Medicine

Background:

• Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory conditions lacking effective pharmacological treatments.
• Dynasore, a GTPase inhibitor, shows promise in various disease models.
• The efficacy of dynasore in lipopolysaccharide (LPS)-induced ALI remains unexplored.

Purpose of the Study:

• To investigate the effects of dynasore on macrophage activation in LPS-induced ALI.
• To elucidate the underlying mechanisms of dynasore's action in ALI.
• To explore dynasore as a potential therapeutic agent for ALI/ARDS.

Main Methods:

• Macrophages were activated with LPS and ATP; a mouse ALI model was induced via LPS instillation.
• Key proteins (NLRP3, caspase-1, GSDMD) and inflammatory mediators (cytokines) were quantified.
• Lung tissue morphology and protein distribution were assessed using histology and immunofluorescence.

Main Results:

• Dynasore suppressed NF-κB signaling and reduced pro-inflammatory cytokine production in vitro.
• It inhibited NLRP3 inflammasome activation and macrophage pyroptosis via the Drp1/ROS/NLRP3 axis.
• Dynasore significantly reduced lung injury scores and inflammatory markers in vivo, including IL-1β and IL-6.

Conclusions:

• Dynasore effectively alleviates LPS-induced ALI by modulating macrophage pyroptosis.
• The findings highlight dynasore's potential as a novel therapeutic strategy for ALI and ARDS.