Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes

Li Zheng1, Wenyu Zhou1, Yutong Wu1

  • 1Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Insights

Melatonin (MEL) alleviates sepsis-induced acute respiratory distress syndrome (ARDS) by inhibiting the ROS/HIF-1α/GLUT1/NLRP3 pathway in macrophages via the MT1 receptor. This mechanism improves lung injury and survival in mice.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Molecular Biology

Background:

  • Sepsis-induced acute respiratory distress syndrome (ARDS) is a severe condition with no effective treatments.
  • Melatonin (MEL) shows potential for treating sepsis-induced ARDS, but its mechanism is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which melatonin alleviates sepsis-induced ARDS.
  • To investigate the role of the ROS/HIF-1α/GLUT1/NLRP3 pathway in melatonin's protective effects.

Main Methods:

  • Utilized a lipopolysaccharide (LPS)-induced mouse alveolar macrophage cell line (MH-S) model.
  • Investigated the effects of melatonin on NLRP3 inflammasome activation, glucose transporter 1 (GLUT1) expression, and hypoxia-inducible factor 1 (HIF-1α) levels.
  • Examined the role of reactive oxygen species (ROS) and melatonin receptor 1A (MT1) in melatonin's action.
  • Validated findings in an in vivo mouse model of LPS-induced lung injury.

Main Results:

  • Melatonin inhibited NLRP3 inflammasome activation in LPS-treated macrophages.
  • Melatonin downregulated GLUT1 by inhibiting HIF-1α, an effect modulated by ROS.
  • Melatonin's protective effect was dependent on the MT1 receptor.
  • In vivo, melatonin ameliorated LPS-induced lung injury and improved survival by downregulating the HIF-1α/GLUT1/NLRP3 pathway.

Conclusions:

  • Melatonin exerts protective effects against sepsis-induced ARDS by regulating the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages.
  • The MT1 receptor mediates melatonin's action in this pathway.
  • These findings provide a mechanistic basis for melatonin as a potential therapeutic agent for sepsis-induced ARDS.

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