ArticlePloS one2013
Febuxostat, an inhibitor of xanthine oxidase, suppresses lipopolysaccharide-induced MCP-1 production via MAPK phosphatase-1-mediated inactivation of JNK.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 83 citations in OpenAlex.
- Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators.Scientific reports · 2024Trial
- Effects of Febuxostat Therapy on Circulating Adipokine Profiles in Patients with Overweight or Obesity and Asymptomatic Hyperuricemia: A Randomized Controlled Study.Obesity facts · 2024Trial
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- The Role of the Intestinal Microbiome in the Pathogenesis and Treatment of Hyperuricemia: A Review.Food science & nutrition · 2025Review
- Management of intraocular pressure and inflammation using febuxostat film:ADMET & DMPK · 2025Article
- WN1703 alleviates gout symptoms via inflammatory signaling pathways in an acute gout rat model.Pharmaceutical science advances · 2024Article
- Association of xanthine oxidoreductase inhibitor use with insulin secretory capacity in patients with type 2 diabetes.Journal of diabetes investigation · 2024Article
- Purinosomes and Purine Metabolism in Mammalian Neural Development: A Review.Acta histochemica et cytochemica · 2024Review
- Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement activation and inflammation modulators.Research square · 2024Article
- Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.Cell communication and signaling : CCS · 2024Review
- Sustained xanthine oxidase inhibitor treat to target urate lowering therapy rewires a tight inflammation serum protein interactome.Research square · 2024Article
- The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2.Antioxidants (Basel, Switzerland) · 2023Article
- Soy Phospholipids Exert a Renoprotective Effect by Inhibiting the Nuclear Factor Kappa B Pathway in Macrophages.Metabolites · 2022Article
- Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms.Frontiers in pharmacology · 2022Review
- The protective effect of natural medicines against excessive inflammation and oxidative stress in acute lung injury by regulating the Nrf2 signaling pathway.Frontiers in pharmacology · 2022Review
- Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis.International journal of molecular sciences · 2021Review
- Whitening and inhibiting NF-κB-mediated inflammation properties of the biotransformed green ginseng berry of new cultivar K1, ginsenoside Rg2 enriched, on B16 and LPS-stimulated RAW 264.7 cells.Journal of ginseng research · 2021Article
- Hyperuricemia and the Risk of Heart Failure: Pathophysiology and Therapeutic Implications.Frontiers in endocrinology · 2021Review
- The Crucial Role of Xanthine Oxidase in CKD Progression Associated with Hypercholesterolemia.International journal of molecular sciences · 2020Article
- A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess reactive oxygen species (ROS) formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO) is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes.
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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.