ArticleClinical science (London, England : 1979)2015
PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice.
Article in Clinical science (London, England : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.Respiratory medicineTrial
- Cleavage and inactivation of poly(ADP-ribose) polymerase in peripheral blood mononuclear cells of patients with acute respiratory distress syndrome.Respiratory research · 2026Article
- Anoikis-related biomarkers PARP1 and SDCBP as diagnostic and therapeutic targets for asthma.Scientific reports · 2025Article
- Distinct single-cell transcriptional profile in CD4+ T-lymphocytes among obese children with asthma.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.Clinical science (London, England : 1979) · 2023Review
- Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy.Journal of translational medicine · 2022Article
- Selective Pharmaceutical Inhibition of PARP14 Mitigates Allergen-Induced IgE and Mucus Overproduction in a Mouse Model of Pulmonary Allergic Response.ImmunoHorizons · 2022Article
- MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- The potential of PARP inhibitors in targeted cancer therapy and immunotherapy.Frontiers in molecular biosciences · 2022Review
- Plasma Extracellular Vesicle miRNA Profiles Distinguish Chronic Obstructive Pulmonary Disease Exacerbations and Disease Severity.International journal of chronic obstructive pulmonary disease · 2022Article
- COVID-19 and pulmonary fibrosis: therapeutics in clinical trials, repurposing, and potential development.Archives of pharmacal research · 2021Review
- PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis.Journal of inflammation research · 2021Review
- The Interaction Between Pulmonary Fibrosis and COVID-19 and the Application of Related Anti-Fibrotic Drugs.Frontiers in pharmacology · 2021Review
- Targeting PARP-1 with metronomic therapy modulates MDSC suppressive function and enhances anti-PD-1 immunotherapy in colon cancer.Journal for immunotherapy of cancer · 2021Article
- Poly(ADP-Ribose) Polymerase Inhibition in Acute Lung Injury. A Reemerging Concept.American journal of respiratory cell and molecular biology · 2020Review
- Poly(ADP-ribose) polymerase inhibition: past, present and future.Nature reviews. Drug discovery · 2020Review
- Repositioning PARP inhibitors for SARS-CoV-2 infection(COVID-19); a new multi-pronged therapy for acute respiratory distress syndrome?British journal of pharmacology · 2020Review
- Role of CD38/cADPR signaling in obstructive pulmonary diseases.Current opinion in pharmacology · 2020Review
- miR-223: A Key Regulator in the Innate Immune Response in Asthma and COPD.Frontiers in medicine · 2020Review
- Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Our laboratory established a role for poly(ADP-ribose)polymerase (PARP) in asthma. To increase the clinical significance of our studies, it is imperative to demonstrate that PARP is actually activated in human asthma, to examine whether a PARP inhibitor approved for human testing such as olaparib blocks already-established chronic asthma traits in response to house dust mite (HDM), a true human allergen, in mice and to examine whether the drug modulates human cluster of differentiation type 4 (CD4(+)) T-cell function. To conduct the study, human lung specimens and peripheral blood mononuclear cells (PBMCs) and a HDM-based mouse asthma model were used. Our results show that PARP is activated in PBMCs and lung tissues of asthmatics. PARP inhibition by olaparib or gene knockout blocked established asthma-like traits in mice chronically exposed to HDM including airway eosinophilia and hyper-responsiveness. These effects were linked to a marked reduction in T helper 2 (Th2) cytokine production without a prominent effect on interferon (IFN)-γ or interleukin (IL)-10. PARP inhibition prevented HDM-induced increase in overall cellularity, weight and CD4(+) T-cell population in spleens of treated mice whereas it increased the T-regulatory cell population. In CD3/CD28-stimulated human CD4 (+)T-cells, olaparib treatment reduced Th2 cytokine production potentially by modulating GATA binding protein-3 (gata-3)/IL-4 expression while moderately affecting T-cell proliferation. PARP inhibition inconsistently increased IL-17 in HDM-exposed mice and CD3/CD28-stimulated CD4(+) T cells without a concomitant increase in factors that can be influenced by IL-17. In the present study, we provide evidence for the first time that PARP-1 is activated in human asthma and that its inhibition is effective in blocking established asthma in mice.
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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.