ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- The Involvement of MicroRNAs in Innate Immunity and Cystic Fibrosis Lung Disease: A Narrative Review.Current issues in molecular biology · 2026Review
- Revolutionizing Autoimmune Research: The Role of Caveolin-1.Immunity, inflammation and disease · 2025Review
- Article
- Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease.Frontiers in immunology · 2023Review
- The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.Clinics in chest medicine · 2022Review
- Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.Progress in retinal and eye research · 2022Review
- Impact ofInternational journal of molecular sciences · 2022Review
- Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis.Experimental & molecular medicine · 2022Article
- Modulating macrophage function to reinforce host innate resistance againstFrontiers in immunology · 2022Review
- Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor-beta expression in chronic rhinosinusitis with nasal polyps.Immunity, inflammation and disease · 2020Article
- Airway Inflammation and Host Responses in the Era of CFTR Modulators.International journal of molecular sciences · 2020Review
- Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for Pseudomonas aeruginosa survival.Scientific reports · 2020Article
- Targeting the Heme Oxygenase 1/Carbon Monoxide Pathway to Resolve Lung Hyper-Inflammation and Restore a Regulated Immune Response in Cystic Fibrosis.Frontiers in pharmacology · 2020Review
- Cystic fibrosis transmembrane conductance regulator (CFTR) and autophagy: hereditary defects in cystic fibrosisOncotarget · 2019Review
- Cystic Fibrosis and Pseudomonas aeruginosa: the Host-Microbe Interface.Clinical microbiology reviews · 2019Review
- Article
- Heme Catabolic Pathway in Inflammation and Immune Disorders.Frontiers in pharmacology · 2019Review
- Article
- Killing of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung InflammationInfection and immunity · 2017Article
- Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
We have previously reported that TLR4 signaling is increased in LPS-stimulated cystic fibrosis (CF) macrophages (MΦs), contributing to the robust production of proinflammatory cytokines. The heme oxygenase-1 (HO-1)/CO pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. In this study, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules enhances CAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations re-established HO-1 and CAV-1 cell surface localization in CF MΦs. Consistent with restoration of HO-1/CAV-1-negative regulation of TLR4 signaling, genetic or pharmacological (CO-releasing molecule 2) induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counterregulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease.
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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.