ArticleJournal of immunology (Baltimore, Md. : 1950)2019
A Dynamic Variation of Pulmonary ACE2 Is Required to Modulate Neutrophilic Inflammation in Response to
Article in Journal of immunology (Baltimore, Md. : 1950), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Associations between COVID-19 and skin conditions identified through epidemiology and genomic studies.The Journal of allergy and clinical immunology · 2021Pooled it
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection.Molecular biotechnology · 2025Review
- Alterations of the gut microbiota in patients with diabetic nephropathy and its association with the renin-angiotensin system.Journal of diabetes and metabolic disorders · 2025Article
- Review
- Advancements in the Development of Anti-SARS-CoV-2 Therapeutics.International journal of molecular sciences · 2024Review
- The Renin-Angiotensin System (RAS) in COVID-19 Disease: Where We Are 3 Years after the Beginning of the Pandemic.Microorganisms · 2024Review
- Discovery, validation, and prodrug design of an ACE2 activator for treating bacterial infection-induced lung inflammation.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog.Biotech (Basel (Switzerland)) · 2023Article
- An integrated multi-omics analysis of identifies distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa.PLoS pathogens · 2023Article
- Interaction Between SARS-CoV-2 and Pathogenic Bacteria.Current microbiology · 2023Review
- Inhibiting the Deubiquitinase UCHL1 Reduces SARS-CoV-2 Viral Uptake by ACE2.American journal of respiratory cell and molecular biology · 2023Article
- Bioinformatics-based investigation on the genetic influence between SARS-CoV-2 infections and idiopathic pulmonary fibrosis (IPF) diseases, and drug repurposing.Scientific reports · 2023Article
- Human ACE2 expression, a major tropism determinant for SARS-CoV-2, is regulated by upstream and intragenic elements.PLoS pathogens · 2023Article
- Article
- Zebrafish models of COVID-19.FEMS microbiology reviews · 2023Review
- Study of kaempferol in the treatment of COVID-19 combined with Chikungunya co-infection by network pharmacology and molecular docking technology.Informatics in medicine unlocked · 2023Article
- Lycopene: a therapeutic strategy against coronavirus disease 19 (COVID- 19).Inflammopharmacology · 2022Review
- Exposure to a mixture of per-and polyfluoroalkyl substances modulates pulmonary expression of ACE2 and circulating hormones and cytokines.Toxicology and applied pharmacology · 2022Article
- Dysregulation of immunity in COVID-19 and SLE.Inflammopharmacology · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Angiotensin-converting enzyme 2 (ACE2) is a potent negative regulator capable of restraining overactivation of the renin-angiotensin system, which contributes to exuberant inflammation after bacterial infection. However, the mechanism through which ACE2 modulates this inflammatory response is not well understood. Accumulating evidence indicates that infectious insults perturb ACE2 activity, allowing for uncontrolled inflammation. In the current study, we demonstrate that pulmonary ACE2 levels are dynamically varied during bacterial lung infection, and the fluctuation is critical in determining the severity of bacterial pneumonia. Specifically, we found that a pre-existing and persistent deficiency of active ACE2 led to excessive neutrophil accumulation in mouse lungs subjected to bacterial infection, resulting in a hyperinflammatory response and lung damage. In contrast, pre-existing and persistent increased ACE2 activity reduces neutrophil infiltration and compromises host defense, leading to overwhelming bacterial infection. Further, we found that the interruption of pulmonary ACE2 restitution in the model of bacterial lung infection delays the recovery process from neutrophilic lung inflammation. We observed the beneficial effects of recombinant ACE2 when administered to bacterially infected mouse lungs following an initial inflammatory response. In seeking to elucidate the mechanisms involved, we discovered that ACE2 inhibits neutrophil infiltration and lung inflammation by limiting IL-17 signaling by reducing the activity of the STAT3 pathway. The results suggest that the alteration of active ACE2 is not only a consequence of bacterial lung infection but also a critical component of host defense through modulation of the innate immune response to bacterial lung infection by regulating neutrophil influx.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.