ArticleThe Journal of allergy and clinical immunology2015
Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03080480 (Efficacy and Safety of Pioglitazone Therapy for Chronic Granulomatous Disease Patients With Severe Infection.), which is not on this map. Cited by 39 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.
Efficacy and Safety of Pioglitazone Therapy for Chronic Granulomatous Disease Patients With Severe Infection.
Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- High Levels of IL-18 and IFN-γ in Chronically Inflamed Tissue in Chronic Granulomatous Disease.Frontiers in immunology · 2019Trial
- Pioglitazone as a novel therapeutic approach in chronic granulomatous disease.The Journal of allergy and clinical immunology · 2016Trial
- NLRP3 inflammasome blockade treats intestinal inflammation associated with chronic granulomatous disease.Blood · 2026Article
- Neutrophil progenitor cell therapy rescues host defense against Staphylococcus aureus in murine chronic granulomatous disease.Journal of leukocyte biology · 2026Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Activation of the MEK1-CHK2 axis in macrophages by Staphylococcus aureus promotes mitophagy, resulting in a reduction in bactericidal efficacy.Molecular medicine (Cambridge, Mass.) · 2025Article
- Innate Immune-Enhancing Effect ofJournal of microbiology and biotechnology · 2024Article
- Review
- A Novel Assay in Whole Blood Demonstrates Restoration of Mitochondrial Activity in Phagocytes After Successful HSCT in Hyperinflamed X-Linked Chronic Granulomatous Disease.Journal of clinical immunology · 2022Article
- Treatment with Polyethylene Glycol-Conjugated Fungal D-Amino Acid Oxidase Reduces Lung Inflammation in a Mouse Model of Chronic Granulomatous Disease.Inflammation · 2022Article
- Chronic Granulomatous Disease: a Comprehensive Review.Clinical reviews in allergy & immunology · 2021Review
- Oxidants in Physiological Processes.Handbook of experimental pharmacology · 2021Review
- Raising the 'Good' Oxidants for Immune Protection.Frontiers in immunology · 2021Review
- Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism.Frontiers in immunology · 2021Review
- The effect of type 2 diabetes on CD36 expression and the uptake of oxLDL: Diabetes affects CD36 and oxLDL uptake.Experimental neurology · 2020Article
- Pioglitazone improves phagocytic activity of liver recruited macrophages in elderly mice possibly by promoting glucose catabolism.Innate immunity · 2019Article
- Myriad Faces of Chronic Granulomatous Disease: All in an Indian Family with Novel CYBB Defect.Journal of clinical immunology · 2019Article
- Review
- Macrophage nuclear receptors: Emerging key players in infectious diseases.PLoS pathogens · 2019Review
- Does Pioglitazone Lead to Neutrophil Extracellular Traps Formation in Chronic Granulomatous Disease Patients?Frontiers in immunology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDeficient production of reactive oxygen species (ROS) by the phagocyte nicotinamide adenine dinucleotide (NADPH) oxidase in patients with chronic granulomatous disease (CGD) results in susceptibility to certain pathogens secondary to impaired oxidative killing and mobilization of other phagocyte defenses. Peroxisome proliferator-activated receptor (PPAR) γ agonists, including pioglitazone, approved for type 2 diabetes therapy alter cellular metabolism and can heighten ROS production. It was hypothesized that pioglitazone treatment of gp91(phox-/-) mice, a murine model of human CGD, would enhance phagocyte oxidant production and killing of Staphylococcus aureus, a significant pathogen in patients with this disorder.
objectivesWe sought to determine whether pioglitazone treatment of gp91(phox-/-) mice enhanced phagocyte oxidant production and host defense.
methodsWild-type and gp91(phox-/-) mice were treated with the PPARγ agonist pioglitazone, and phagocyte ROS and killing of S aureus were investigated.
resultsAs demonstrated by 3 different ROS-sensing probes, short-term treatment of gp91(phox-/-) mice with pioglitazone enhanced stimulated ROS production in neutrophils and monocytes from blood and neutrophils and inflammatory macrophages recruited to tissues. Mitochondria were identified as the source of ROS. Findings were replicated in human monocytes from patients with CGD after ex vivo pioglitazone treatment. Importantly, although mitochondrial (mt)ROS were deficient in gp91(phox-/-) phagocytes, their restoration with treatment significantly enabled killing of S aureus both ex vivo and in vivo.
conclusionsTogether, the data support the hypothesis that signaling from the NADPH oxidase under normal circumstances governs phagocyte mtROS production and that such signaling is lacking in the absence of a functioning phagocyte oxidase. PPARγ agonism appears to bypass the need for the NADPH oxidase for enhanced mtROS production and partially restores host defense in CGD.
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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.