ArticleAllergy2011
PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model.
Article in Allergy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway.iScience · 2024Article
- Expanding the Perspective on PARP1 and Its Inhibitors in Cancer Therapy: From DNA Damage Repair to Immunomodulation.Biomedicines · 2024Review
- The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy.Bioscience reports · 2023Article
- PARP2 promotes inflammation in psoriasis by modulating estradiol biosynthesis in keratinocytes.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Review
- 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
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- Review
- CD38: T Cell Immuno-Metabolic Modulator.Cells · 2020Review
- The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism.Genes & development · 2020Review
- miR-223: A Key Regulator in the Innate Immune Response in Asthma and COPD.Frontiers in medicine · 2020Review
- The Role of PARPs in Inflammation-and Metabolic-Related Diseases: Molecular Mechanisms and Beyond.Cells · 2019Review
- Novel insights into PARPs in gene expression: regulation of RNA metabolism.Cellular and molecular life sciences : CMLS · 2019Review
- PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function.Mediators of inflammation · 2019Article
- Pediatric Eosinophilic Esophagitis Endotypes: Are We Closer to Predicting Treatment Response?Clinical reviews in allergy & immunology · 2018Review
- Asthma and poly(ADP-ribose) polymerase inhibition: a new therapeutic approach.Drug design, development and therapy · 2018Review
- Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review.Frontiers in immunology · 2017Review
- Calpain inhibition as a possible new therapeutic target in multiple sclerosis.AIMS molecular science · 2017Article
- Dual roles of calpain in facilitating Coxsackievirus B3 replication and prompting inflammation in acute myocarditis.International journal of cardiology · 2016Article
- STAT6 and PARP Family Members in the Development of T Cell-dependent Allergic Inflammation.Immune network · 2016Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWe recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1(-/-) mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5.
objectiveTo explore the mechanism by which PARP-1 regulates IL-5 production and to determine how PARP-1 inhibition blocks allergen-induced eosinophilia.
methodsThis study was conducted using a murine model of allergic airway inflammation and primary splenocytes.
resultsPARP-1 knockout-associated reduction in IL-5 upon allergen exposure occurs at the mRNA level. Such an effect appears to take place after IL-4 receptor activation as PARP-1 inhibition exerted no effect on JAK1/JAK3 activation. Signal transducer and activator of transcription-6 (STAT-6) protein was severely downregulated in spleens of PARP-1(-/-) mice without any effect on mRNA levels, suggesting an effect on protein integrity rather than gene transcription. Interestingly, the degradation of STAT-6 in PARP-1(-/-) mice required allergen stimulation. Additionally, PARP-1 enzymatic activity appears to be required for STAT-6 integrity. The downregulation of STAT-6 coincided with mRNA and protein reduction of GATA-binding protein-3 and occupancy of its binding site on the IL-5 gene promoter. IL-4 was sufficient to induce STAT-6 downregulation in both PARP-1(-/-) mice and isolated splenocytes. Such degradation may be mediated by calpain, but not by proteasomes.
conclusionThese results demonstrate a novel function of PARP-1 in regulating IL-5 expression during allergen-induced inflammation and explain the underlying mechanism by which PARP-1 inhibition results in IL-5 reduction.
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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.