ArticleThe Journal of clinical investigation2011
Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 133 citations in OpenAlex.
- Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.Frontiers in immunology · 2026Review
- Effect of allyl isothiocyanate on 4-HNE induced glucocorticoid resistance in COPD and the underlying mechanism.Heliyon · 2024Article
- Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane.Biomedicines · 2024Review
- Prospect of thioredoxin as a possibly effective tool to combat OSAHS.Sleep & breathing = Schlaf & Atmung · 2023Review
- The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway.Antioxidants (Basel, Switzerland) · 2023Review
- Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review.Molecules (Basel, Switzerland) · 2022Review
- Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Pathological Mechanism and Targeted Drugs of COPD.International journal of chronic obstructive pulmonary disease · 2022Review
- Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- CpG oligodeoxynucleotides attenuate RORγt-mediated Th17 response by restoring histone deacetylase-2 in cigarette smoke-exposure asthma.Cell & bioscience · 2021Article
- Progress in the mechanism and targeted drug therapy for COPD.Signal transduction and targeted therapy · 2020Review
- UPLC-QTOF-MS-guided isolation of anti-COPD ginsenosides from wild ginseng.RSC advances · 2019Article
- Carbocisteine Improves Histone Deacetylase 2 Deacetylation Activity via Regulating Sumoylation of Histone Deacetylase 2 in Human Tracheobronchial Epithelial Cells.Frontiers in pharmacology · 2019Article
- Extraction, identification, and antioxidant property evaluation of limonin from pummelo seeds.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2018Article
- Jinwei Tang modulates HDAC2 expression in a rat model of COPD.Experimental and therapeutic medicine · 2018Article
- Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease.Oxidative medicine and cellular longevity · 2018Review
- Emerging pharmaceutical therapies for COPD.International journal of chronic obstructive pulmonary disease · 2017Review
- Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review.Frontiers in immunology · 2017Review
- New Insights in Glucocorticoid Receptor Signaling-More Than Just a Ligand-Binding Receptor.Frontiers in endocrinology · 2017Review
Corrections and comments
- Retraction · 2014-12-01Manipulation of Images · Objections by Third Party ·
- Commented on by
- Retracted
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic obstructive pulmonary disease (COPD), which is caused primarily by cigarette smoking, is a major health problem worldwide. The progressive decline in lung function that occurs in COPD is a result of persistent inflammation of the airways and destruction of the lung parenchyma. Despite the key role of inflammation in the pathogenesis of COPD, treatment with corticosteroids - normally highly effective antiinflammatory drugs - has little therapeutic benefit. This corticosteroid resistance is largely caused by inactivation of histone deacetylase 2 (HDAC2), which is critical for the transrepressive activity of the glucocorticoid receptor (GR) that mediates the antiinflammatory effect of corticosteroids. Here, we show that in alveolar macrophages from patients with COPD, S-nitrosylation of HDAC2 is increased and that this abolishes its GR-transrepression activity and promotes corticosteroid insensitivity. Cys-262 and Cys-274 of HDAC2 were found to be the targets of S-nitrosylation, and exogenous glutathione treatment of macrophages from individuals with COPD restored HDAC2 activity. Treatment with sulforaphane, a small-molecule activator of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), was also able to denitrosylate HDAC2, restoring dexamethasone sensitivity in alveolar macrophages from patients with COPD. These effects of sulforaphane were glutathione dependent. We conclude that NRF2 is a novel drug target for reversing corticosteroid resistance in COPD and other corticosteroid-resistant inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.