ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Cholesterol-mediated inflammation activation in alveolar macrophages.BMC biology · 2025Article
- Cholesterol Accumulation Enhances Cigarette Smoke-Induced Airway Epithelial Inflammation.International journal of chronic obstructive pulmonary disease · 2025Article
- Exploring the molecular mechanisms of asthma across multiple datasets.Annals of medicine · 2024Article
- Activation of LXR signaling ameliorates apoptosis of alveolar epithelial cells in Bronchopulmonary dysplasia.Respiratory research · 2024Article
- Network pharmacology, molecular docking, and untargeted metabolomics reveal molecular mechanisms of multi-targets effects of Qingfei Tongluo Plaster improving respiratory syncytial virus pneumonia.Chinese herbal medicines · 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
- Potential of gut microbiota metabolites in treating COPD: network pharmacology and Mendelian randomization approaches.Frontiers in microbiology · 2024Article
- Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD.JCI insight · 2023Article
- The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2023Review
- The Relationship of Cholesterol Responses to Mitochondrial Dysfunction and Lung Inflammation in Chronic Obstructive Pulmonary Disease.Medicina (Kaunas, Lithuania) · 2023Review
- Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.Frontiers in immunology · 2023Article
- MicroRNA Control Lipid-laden Alveolar Macrophages in Smokers: A Potential Therapeutic Target for Chronic Obstructive Pulmonary Disease?American journal of respiratory cell and molecular biology · 2022Article
- NLRP3 Inflammasome Priming and Activation Are Regulated by a Phosphatidylinositol-Dependent Mechanism.ImmunoHorizons · 2022Article
- High-Density Lipoproteins: A Role in Inflammation in COPD.International journal of molecular sciences · 2022Review
- Bioinformatic Analysis ofMembranes · 2021Article
- Molecular Mechanisms of Lipid Metabolism Disorders in Infectious Exacerbations of Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2021Review
- Suppression of cigarette smoke induced MMP1 expression by selective serotonin re-uptake inhibitors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Role of ABC Transporters in Lipid Metabolism and the Comorbid Course of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2021Review
- Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo.Clinical oral investigations · 2021Article
- Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice.Environmental health perspectives · 2021Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Macrophage infiltration is common to both emphysema and atherosclerosis, and cigarette smoke down-regulates the macrophage cholesterol efflux transporter ATP binding cassette (ABC)A1. This decreased cholesterol efflux results in lipid-laden macrophages. We hypothesize that cigarette smoke adversely affects cholesterol transport via an ABCA1-dependent mechanism in macrophages, enhancing TLR4/myeloid differentiation primary response gene 88 (Myd88) signaling and resulting in matrix metalloproteinase (MMP) up-regulation and exacerbation of pulmonary inflammation. ABCA1 is significantly down-regulated in the lung upon smoke exposure conditions. Macrophages exposed to cigarette smoke in vivo and in vitro exhibit impaired cholesterol efflux correlating with significantly decreased ABCA1 expression, up-regulation of the TLR4/Myd88 pathway, and downstream MMP-9 and MMP-13 expression. Treatment with liver X receptor (LXR) agonist restores ABCA1 expression after short-term smoke exposure and attenuates the inflammatory response; after long-term smoke exposure, there is also attenuated physiologic and morphologic changes of emphysema. In vitro, treatment with LXR agonist decreases macrophage inflammatory activation in wild-type but not ABCA1 knockout mice, suggesting an ABCA1-dependent mechanism of action. These studies demonstrate an important association between cigarette smoke exposure and cholesterol-mediated pathways in the macrophage inflammatory response. Modulation of these pathways through manipulation of ABCA1 activity effectively blocks cigarette smoke-induced inflammation and provides a potential novel therapeutic approach for the treatment of chronic obstructive pulmonary disease.-Sonett, J., Goldklang, M., Sklepkiewicz, P., Gerber, A., Trischler, J., Zelonina, T., Westerterp, M., Lemaître, V., Okada, V., D'Armiento, J. A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.
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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.