ArticleFree radical biology & medicine2016
Role of NOS2 in pulmonary injury and repair in response to bleomycin.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Radiation-induced Lung Injury (RILI) in Non-human Primates (NHPs) Induces Cellular Senescence and Upregulation of Tyrosine Kinase Fgr, which is Detectable in Bronchoalveolar Lavage.Radiation research · 2025Article
- Targeting Arginine Metabolism in Immune Cells for the Treatment of Pulmonary Inflammatory Diseases.Current allergy and asthma reports · 2025Review
- Is Inducible Nitric Oxide Synthase (iNOS) Promising as a New Target Against Pulmonary Hypertension?Antioxidants (Basel, Switzerland) · 2025Review
- Synthesis and Anti-Inflammatory Activity of Ferulic Acid-Sesquiterpene Lactone Hybrids.Molecules (Basel, Switzerland) · 2024Article
- Aconitate decarboxylase 1 mediates the acute airway inflammatory response to environmental exposures.Frontiers in immunology · 2024Article
- Haploinsufficiency of Cnot3 Aggravates Acid-Induced Acute Lung Injury Likely Through Transcriptional and Post-Transcriptional Upregulation of Pro-Inflammatory Genes.Journal of inflammation research · 2024Article
- Intratracheal Administration of Acyl Coenzyme A Acyltransferase-1 Inhibitor K-604 Reduces Pulmonary Inflammation Following Bleomycin-Induced Lung Injury.The Journal of pharmacology and experimental therapeutics · 2022Article
- Myeloid cell dynamics in bleomycin-induced pulmonary injury in mice; effects of anti-TNFα antibody.Toxicology and applied pharmacology · 2021Article
- Deficiency of the novel high mobility group protein HMGXB4 protects against systemic inflammation-induced endotoxemia in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell Origin and iNOS Function Are Critical to Macrophage Activation Following Acute Lung Injury.Frontiers in pharmacology · 2021Article
- Fatty acid nitroalkenes inhibit the inflammatory response to bleomycin-mediated lung injury.Toxicology and applied pharmacology · 2020Article
- Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Nitric Oxide Regulates Macrophage Fungicidal ActivityApplied in vitro toxicology · 2020Article
- Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled byAmerican journal of physiology. Lung cellular and molecular physiology · 2019Article
- Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers.International journal of environmental research and public health · 2019Article
- Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Regulation of ezrin tension by S-nitrosylation mediates non-small cell lung cancer invasion and metastasis.Theranostics · 2019Article
- S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination.Frontiers in immunology · 2019Article
- Protective Role of Surfactant Protein-D Against Lung Injury and Oxidative Stress Induced by Nitrogen Mustard.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Nitric oxide (NO) is derived from multiple isoforms of the Nitric Oxide Synthases (NOSs) within the lung for a variety of functions; however, NOS2-derived nitrogen oxides seem to play an important role in inflammatory regulation. In this study, we investigate the role of NOS2 in pulmonary inflammation/fibrosis in response to intratracheal bleomycin instillation (ITB) and to determine if these effects are related to macrophage phenotype. Systemic NOS2 inhibition was achieved by administration of 1400W, a specific and potent NOS2 inhibitor, via osmotic pump starting six days prior to ITB. 1400W administration attenuated lung inflammation, decreased chemotactic activity of the broncheoalveolar lavage (BAL), and reduced BAL cell count and nitrogen oxide production. S-nitrosylated SP-D (SNO-SP-D), which has a pro-inflammatory function, was formed in response to ITB; but this formation, as well as structural disruption of SP-D, was inhibited by 1400W. mRNA levels of IL-1β, CCL2 and Ptgs2 were decreased by 1400W treatment. In contrast, expression of genes associated with alternate macrophage activation and fibrosis Fizz1, TGF-β and Ym-1 was not changed by 1400W. Similar to the effects of 1400W, NOS2-/- mice displayed an attenuated inflammatory response to ITB (day 3 and day 8 post-instillation). The DNA-binding activity of NF-κB was attenuated in NOS2-/- mice; in addition, expression of alternate activation genes (Fizz1, Ym-1, Gal3, Arg1) was increased. This shift towards an increase in alternate activation was confirmed by western blot for Fizz-1 and Gal-3 that show persistent up-regulation 15 days after ITB. In contrast arginase, which is increased in expression at 8 days post ITB in NOS2-/-, resolves by day 15. These data suggest that NOS2, while critical to the development of the acute inflammatory response to injury, is also necessary to control the late phase response to ITB.
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Registered trials
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