ArticleOxidative medicine and cellular longevity2022
Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury.
Article in Oxidative medicine and cellular longevity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Physiological relevance of autocrine melatonin signaling in pineal and extrapineal sites: a systematic review.Function (Oxford, England) · 2026Pooled it
- Targeting alveolar macrophages: a promising intervention for pulmonary infection and acute lung injury.Cellular & molecular biology letters · 2025Review
- Targeting Lung Damage: Amniotic Mesenchymal Stem Cells Mitigate Lipopolysaccharide-Induced Acute Lung Injury via Multiple Signaling Pathways.International journal of molecular sciences · 2025Article
- Macrophage pyroptosis mediates hyperoxia-induced inflammatory lung injury in neonates.Frontiers in immunology · 2025Article
- Melatonin ameliorates inflammation-induced developmental defects of enamel by upregulating regulator of G protein signaling 2.Journal of dental sciences · 2024Article
- Review
- Large-Scale Isolation of Milk Exosomes for Skincare.Pharmaceutics · 2024Article
- Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.Respiratory research · 2024Article
- Role of Melatonin in Viral, Bacterial and Parasitic Infections.Biomolecules · 2024Review
- Unlocking the potential ofFrontiers in microbiology · 2024Article
- Melatonin in animal husbandry: functions and applications.Frontiers in veterinary science · 2024Review
- Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies.Cardiovascular toxicology · 2023Review
- The Effects of Viruses on Insulin Sensitivity and Blood-Brain Barrier Function.International journal of molecular sciences · 2023Review
- Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses.Exploration of targeted anti-tumor therapy · 2023Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza virus infection is one of the strongest pathogenic factors for the development of acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS). However, the underlying cellular and molecular mechanisms have not been clarified. In this study, we aim to investigate whether melatonin modulates macrophage polarization, oxidative stress, and pyroptosis via activating Apolipoprotein E/low-density lipoprotein receptor (ApoE/LDLR) pathway in influenza A-induced ALI. Here, wild-type (WT) and ApoE-/- mice were instilled intratracheally with influenza A (H3N2) and injected intraperitoneally with melatonin for 7 consecutive days. In vitro, WT and ApoE-/- murine bone marrow-derived macrophages (BMDMs) were pretreated with melatonin before H3N2 stimulation. The results showed that melatonin administration significantly attenuated H3N2-induced pulmonary damage, leukocyte infiltration, and edema; decreased the expression of proinflammatory M1 markers; enhanced anti-inflammatory M2 markers; and switched the polarization of alveolar macrophages (AMs) from M1 to M2 phenotype. Additionally, melatonin inhibited reactive oxygen species- (ROS-) mediated pyroptosis shown by downregulation of malonaldehyde (MDA) and ROS levels as well as inhibition of the NLRP3/GSDMD pathway and lactate dehydrogenase (LDH) release. Strikingly, the ApoE/LDLR pathway was activated when melatonin was applied in H3N2-infected macrophages and mice. ApoE knockout mostly abrogated the protective impacts of melatonin on H3N2-induced ALI and its regulatory ability on macrophage polarization, oxidative stress, and pyroptosis. Furthermore, recombinant ApoE3 (re-ApoE3) inhibited H3N2-induced M1 polarization of BMDMs with upregulation of MT1 and MT2 expression, but re-ApoE2 and re-ApoE4 failed to do this. Melatonin combined with re-ApoE3 played more beneficial protective effects on modulating macrophage polarization, oxidative stress, and pyroptosis in H3N2-infected ApoE-/- BMDMs. Our study indicated that melatonin attenuated influenza A- (H3N2-) induced ALI by inhibiting the M1 polarization of pulmonary macrophages and ROS-mediated pyroptosis via activating the ApoE/LDLR pathway. This study suggested that melatonin-ApoE/LDLR axis may serve as a novel therapeutic strategy for influenza virus-induced ALI.
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