ArticleBiomolecules2022
Inhibition of STAT6 Activation by AS1517499 Inhibits Expression and Activity of PPARγ in Macrophages to Resolve Acute Inflammation in Mice.
Article in Biomolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Eicosapentaenoic Acid Attenuates Inflammation in an LPS-Induced Mouse Model of Mastitis Partly Through Modulation of the PPARγ-NF-κB Signaling Pathway.Biomolecules · 2026Article
- Apoptotic extracellular vesicles derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by enhancing cell activity and regulating immunity microenvironment.Materials today. Bio · 2026Article
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- SLC25A1-Mediated Cholesterol Accumulation Promotes Endometriosis Progression by Enhancing Endometrial Stromal Cell Proliferation, Invasion, and M2 Macrophage Polarization.International journal of biological sciences · 2026Article
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- Ginsenoside Rg1 attenuates asthma features in mice co-exposed to house dust mite allergen and diesel exhaust particle by modulating epithelial ILC2 interactions.Journal of ginseng research · 2026Article
- Identifying Myeloid-Derived Suppressor Cells and Lipocalin-2 as Therapeutic Targets for Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Human Tendon-on-a-Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis.Advanced healthcare materials · 2025Article
- Immunomodulatory Effects and Mechanisms of Two-Dimensional Black Phosphorus on Macrophage Polarization and Bone Regeneration.International journal of nanomedicine · 2025Review
- Alpha-galactosylceramide pre-treatment attenuates clinical symptoms of LPS-induced acute neuroinflammation by converting pathogenic iNKT cells to anti-inflammatory iNKT10 cells in the brain.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- S100A9 deletion in microglia/macrophages ameliorates brain injury through the STAT6/PPARγ pathway in ischemic stroke.CNS neuroscience & therapeutics · 2024Article
- Article
- Review
- Zymosan-Induced Murine Peritonitis Is Associated with an Increased Sphingolipid Synthesis without Changing the Long to Very Long Chain Ceramide Ratio.International journal of molecular sciences · 2023Article
- Jak2/STAT6/c-Myc pathway is vital to the pathogenicity of Philadelphia-positive acute lymphoblastic leukemia caused by P190Cell communication and signaling : CCS · 2023Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transducer and activator of transcription 6 (STAT6) promotes an anti-inflammatory process by inducing the development of M2 macrophages. We investigated whether modulating STAT6 activity in macrophages using AS1517499, the specific STAT6 inhibitor, affects the restoration of homeostasis after an inflammatory insult by regulating PPARγ expression and activity. Administration of AS1517499 suppressed the enhanced STAT6 phosphorylation and nuclear translocation observed in peritoneal macrophages after zymosan injection. In addition, AS1517499 delayed resolution of acute inflammation as evidenced by enhanced secretion of pro-inflammatory cytokines, reduced secretion of anti-inflammatory cytokines in PLF and supernatants from peritoneal macrophages, and exaggerated neutrophil numbers and total protein levels in PLF. We demonstrate temporal increases in annexin A1 (AnxA1) protein and mRNA levels in peritoneal lavage fluid (PLF), peritoneal macrophages, and spleen in a murine model of zymosan-induced acute peritonitis. In vitro priming of mouse bone marrow-derived macrophages (BMDM) and peritoneal macrophages with AnxA1 induced STAT6 activation with enhanced PPARγ expression and activity. Using AS1517499, we demonstrate that inhibition of STAT6 activation delayed recovery of PPARγ expression and activity, as well as impaired efferocytosis. Taken together, these results suggest that activation of the STAT6 signaling pathway mediates PPARγ expression and activation in macrophages to resolve acute inflammation.
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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 Socratic graph.