ArticleJournal of leukocyte biology2022
ADAM17/MMP inhibition prevents neutrophilia and lung injury in a mouse model of COVID-19.
Article in Journal of leukocyte biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- Mapping cellular signaling pathways involved in SARS-CoV-2 spike protein-mediated syncytia formation.Infectious diseases & immunity · 2026Article
- Assessment of Selected Biochemical Parameters of the Renin-Angiotensin-Aldosterone System in Repeat Convalescent Plasma Donors in the Context of Long-Term Changes Following SARS-CoV-2 Infection.Journal of clinical medicine · 2025Article
- ADAM17/PTGS2 Facilitates Pulmonary Fibrosis by Regulating Ferroptosis.Journal of cellular and molecular medicine · 2025Article
- Analysis of Biomarker Levels in Nasopharyngeal Swabs, Serum, and Saliva Across Different Health Conditions.Life (Basel, Switzerland) · 2025Article
- Relationship Between Systemic Inflammatory Response Exponents, Levels of ADAM10, ADAM17 Proteins and Selected Clinical Parameters in Patients with Colorectal Cancer: Original Research Study.International journal of molecular sciences · 2025Article
- Potential Mechanisms Underlying COVID-19-Mediated Central and Peripheral Demyelination: Roles of the RAAS and ADAM-17.Molecular neurobiology · 2025Review
- Progress of ADAM17 in Fibrosis-Related Diseases.Mediators of inflammation · 2025Review
- Article
- Targeting iRhom2/ADAM17 attenuates COVID-19-induced cytokine release from cultured lung epithelial cells.Biochemistry and biophysics reports · 2024Article
- Efferocytosis and Respiratory Disease.International journal of molecular sciences · 2023Review
- Natural Killer Cell-Derived Interferon-γ Regulates Macrophage-Mediated Immunopathology During Viral Infection.The Journal of infectious diseases · 2023Article
- Article
- Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?British journal of pharmacology · 2023Article
- Role of the extracellular matrix in COVID-19.World journal of clinical cases · 2023Review
- SARS-CoV-2 and Hypertension: Evidence Supporting Invasion into the Brain Via Baroreflex Circuitry and the Role of Imbalanced Renin-Angiotensin-Aldosterone-System.Neuroscience insights · 2023Article
- Neutrophil heterogeneity and aging: implications for COVID-19 and wound healing.Frontiers in immunology · 2023Review
- Characterization of the angiotensin-converting enzyme 2 (ACE2), the main receptor for the SARS-CoV-2 virus.American journal of clinical and experimental immunology · 2023Review
- New insights into mechanisms of endothelial insulin resistance in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2022Review
- Host Genetic Risk Factors Associated with COVID-19 Susceptibility and Severity in Vietnamese.Genes · 2022Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized by lung injury, cytokine storm, and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe COVID-19 in infected individuals. Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2, the virus causing COVID-19, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates COVID-19-related lung inflammation. We employed a preclinical mouse model using intratracheal instillation of a combination of polyinosinic:polycytidylic acid (poly(I:C)) and the receptor-binding domain of the SARS-CoV-2 spike protein (RBD-S) to mimic lung damage associated with COVID-19. Histologic analysis of inflamed mice confirmed the expected signs of lung injury including edema, fibrosis, vascular congestion, and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill COVID-19 patients. Administration of the ADAM17/MMP inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of proinflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17/MMP inhibition. Thus, we propose inhibition of ADAM17/MMP as a novel promising treatment strategy in SARS-CoV-2-infected individuals to prevent the progression toward severe COVID-19.
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Registered trials
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