ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Regulation of Lung Macrophage Activation and Oxidative Stress Following Ozone Exposure by Farnesoid X Receptor.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Lung injury, oxidative stress, and impaired functioning in a model of prolonged ozone exposure in female mice are associated with macrophage proinflammatory and profibrotic activation and altered bioenergetics.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.BMC medicine · 2025Article
- Parenchymal and inflammatory responses to ozone exposure in the aging healthy and surfactant protein C mutant lung.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Inhaled ozone induces distinct alterations in pulmonary function in models of acute and episodic exposure in female mice.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Farnesoid X receptor (FXR) as a potential therapeutic target for lung diseases: a narrative review.Journal of thoracic disease · 2024Review
- Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- FXR deletion attenuates intestinal barrier dysfunction in murine acute intestinal inflammation.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Transcriptomic-based roadmap to the healthy and ozone-exposed lung.Current opinion in toxicology · 2024Article
- Suppression of Lung Oxidative Stress, Inflammation, and Fibrosis following Nitrogen Mustard Exposure by the Selective Farnesoid X Receptor Agonist Obeticholic Acid.The Journal of pharmacology and experimental therapeutics · 2024Article
- Role of PPARγ in dyslipidemia and altered pulmonary functioning in mice following ozone exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Novel method to assess resident alveolar macrophage efferocytosis of apoptotic neutrophils by flow cytometry.Toxicology and applied pharmacology · 2023Article
- Therapeutic role of ursodeoxycholic acid in colitis-associated cancer via gut microbiota modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Farnesoid X receptor regulates lung macrophage activation and injury following nitrogen mustard exposure.Toxicology and applied pharmacology · 2022Article
- Microvesicle-Derived miRNAs Regulate Proinflammatory Macrophage Activation in the Lung Following Ozone Exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Integrative analysis reveals mouse strain-dependent responses to acute ozone exposure associated with airway macrophage transcriptional activity.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Insights on the mechanisms of action of ozone in the medical therapy against COVID-19.International immunopharmacology · 2021Review
- Role of Innate Immune System in Environmental Lung Diseases.Current allergy and asthma reports · 2021Review
- Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory macrophages are known to contribute to ozone toxicity. Farnesoid X receptor (FXR) is a nuclear receptor involved in regulating bile acid and lipid homeostasis; it also exerts anti-inflammatory activity by suppressing macrophage NF-κB. Herein, we analyzed the role of FXR in regulating macrophage activation in the lung following ozone exposure. Treatment of wild-type (WT) mice with ozone (0.8 ppm, 3 h) resulted in increases in proinflammatory (F4/80+CD11c+CD11b+Ly6CHi) and anti-inflammatory (F4/80+CD11c+CD11b+Ly6CLo) macrophages in the lung. The accumulation of proinflammatory macrophages was increased in FXR-/- mice compared with WT mice; however, anti-inflammatory macrophage activation was blunted as reflected by reduced arginase and mannose receptor expression, a response correlated with decreased Nur77. This was associated with prolonged oxidative stress, as measured by 4-hydroxynonenal-modified proteins in the lung. Loss of FXR was accompanied by protracted increases in lung NF-κB activity and its target, inducible nitric oxide synthase in response to ozone. Levels of Tnf-α, Il-1β, Ccr2, Ccl2, Cx3cr1, and Cx3cl1 were also increased in lungs of FXR-/- relative to WT mice; conversely, genes regulating lipid homeostasis including Lxrα, Apoe, Vldlr, Abcg1, and Abca1 were downregulated, irrespective of ozone exposure. In FXR-/- mice, ozone caused an increase in total lung phospholipids, with no effect on SP-B or SP-D. Dyslipidemia was correlated with blunting of ozone-induced increases in positive end-expiratory pressure-dependent quasi-static pressure volume curves indicating a stiffer lung in FXR-/- mice. These findings identify FXR as a regulator of macrophage activation following ozone exposure suggesting that FXR ligands may be useful in mitigating inflammation and oxidative stress induced by pulmonary irritants.
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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.