ArticleThe Journal of biological chemistry2011
Xanthine oxidoreductase promotes the inflammatory state of mononuclear phagocytes through effects on chemokine expression, peroxisome proliferator-activated receptor-{gamma} sumoylation, and HIF-1{alpha}.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.Journal of advanced research · 2025Review
- Targeting LiverPharmaceutics · 2024Article
- Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- SENP3 facilitates M1 macrophage polarization via the HIF-1α/PKM2 axis in lipopolysaccharide-induced acute lung injury.Innate immunity · 2023Article
- Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes.Biomedicines · 2021Article
- 5-Hydroxymethylfurfural (HMF) levels in honey and other food products: effects on bees and human health.Chemistry Central journal · 2018Review
- Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Xanthine oxidoreductase is required for genotoxic stress-induced NKG2D ligand expression and gemcitabine-mediated antitumor activity.Oncotarget · 2016Article
- Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis.Mediators of inflammation · 2016Review
- The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Linking uric acid metabolism to diabetic complications.World journal of diabetes · 2014Review
- Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function.Scientific reports · 2014Article
- Functions of arginase isoforms in macrophage inflammatory responses: impact on cardiovascular diseases and metabolic disorders.Frontiers in immunology · 2014Review
- The cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells.Journal of diabetes research · 2014Article
- Chemistry meets biology in colitis-associated carcinogenesis.Free radical research · 2013Review
- The risk of heart failure and cardiometabolic complications in obesity may be masked by an apparent healthy status of normal blood glucose.Oxidative medicine and cellular longevity · 2013Article
- The role of xanthine oxidase in hemodialysis-induced oxidative injury: relationship with nutritional status.Oxidative medicine and cellular longevity · 2013Article
- Contribution of uric acid to cancer risk, recurrence, and mortality.Clinical and translational medicine · 2012Article
- Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal.Arthritis and rheumatism · 2012Review
- Untargeted plasma metabolite profiling reveals the broad systemic consequences of xanthine oxidoreductase inactivation in mice.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The protective effects of pharmacological inhibitors of xanthine oxidoreductase (XOR) have implicated XOR in many inflammatory diseases. Nonetheless, the role played by XOR during inflammation is poorly understood. We previously observed that inhibition of XOR within the inflammatory mononuclear phagocytes (MNP) prevented neutrophil recruitment during adoptive transfer demonstrating the role of XOR in MNP-mediated neutrophil recruitment. To further explore the role of XOR in the inflammatory state of MNP, we studied MNP isolated from inflammatory lungs combined with analyses of MNP cell lines. We demonstrated that XOR activity was increased in inflammatory MNP following insufflation of Th-1 cytokines in vivo and that activity was specifically increased by MNP differentiation. Inhibition of XOR reduced levels of CINC-1 secreted by MNP. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in purified rat lung MNP and MNP cell lines reflected both the presence of PPARγ isoforms and PPARγ SUMOylation, and XOR inhibitors increased levels of SUMO-PPARγ in MNP cell lines. Both ectopic overexpression of XOR cDNA and uric acid supplementation reduced SUMO-PPARγ in MNP cells. Levels of the M2 markers CD36, CD206, and arginase-1 were modulated by uric acid and oxonic acid, whereas siRNA to SUMO-1 or PIAS-1 also reduced arginase-1 in RAW264.7 cells. We also observed that HIF-1α was increased by XOR inhibitors in inflammatory MNP and in MNP cell lines. These data demonstrate that XOR promotes the inflammatory state of MNP through effects on chemokine expression, PPARγ SUMOylation, and HIF-1α and suggest that strategies for inhibiting XOR may be valuable in modulating lung inflammatory disorders.
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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.