ArticlePloS one2015
Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- The regulation of COX-2, ABCA1, and ABCG1 by the lncRNA PACERR links the inflammatory response and cholesterol homeostasis.Cell reports · 2026Article
- MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis.Genes and immunity · 2026Article
- Review
- Computational identification of dual COX-1 and NIK inhibitors from marine microalga Chlorella vulgaris.Journal, genetic engineering & biotechnology · 2025Article
- Dynamic changes in macrophage populations and resulting alterations in Prostaglandin ECell communication and signaling : CCS · 2025Article
- Wharton's jelly-derived mesenchymal stem cells ameliorate high altitude-induced heart injury by promoting type 2 macrophage polarization via COX2-PGE2 pathway.Frontiers in immunology · 2025Article
- Releasable, Immune-Instructive, Bioinspired Multilayer Coating Resists Implant-Induced Fibrosis while Accelerating Tissue Repair.Advanced healthcare materials · 2024Article
- Early Gβγ-GRK2 Inhibition Ameliorates Osteoarthritis Development by Simultaneous Anti-Inflammatory and Chondroprotective Effects.International journal of molecular sciences · 2022Article
- Innate Immunity and Cancer Pathophysiology.Annual review of pathology · 2022Review
- Cyclooxygenase-2 Upregulated by Temozolomide in Glioblastoma Cells Is Shuttled In Extracellular Vesicles Modifying Recipient Cell Phenotype.Frontiers in oncology · 2022Article
- Tumor-derived exosomes in the regulation of macrophage polarization.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Review
- Indomethacin augments lipopolysaccharide-induced expression of inflammatory molecules in the mouse brain.PeerJ · 2020Article
- Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy.Journal of translational medicine · 2019Article
- Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model.The Journal of clinical investigation · 2019Article
- Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation.Frontiers in immunology · 2019Review
- Molecular Repolarisation of Tumour-Associated Macrophages.Molecules (Basel, Switzerland) · 2018Review
- Ibuprofen prevents progression of ataxia telangiectasia symptoms in ATM-deficient mice.Journal of neuroinflammation · 2018Article
- Sensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zebrafish.Nature communications · 2018Article
- Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin EScientific reports · 2017Article
- Macrophages and the Recovery from Acute and Chronic Inflammation.Annual review of physiology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX) inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-derived macrophage culture and long-term COX inhibitor treatments in BALB/c mice and zebrafish, we showed that chronic COX inhibition drives macrophages into an inflammatory state. Macrophages differentiated in the presence of SC-560 (COX-1 inhibitor), NS-398 (COX-2 inhibitor) or indomethacin (COX-1/2 inhibitor) for 7 days produced more TNFα or IL-12p70 with enhanced p65/IκB phosphoylation. YmI and IRF4 expression was reduced significantly, indicative of a more inflammatory phenotype. We further observed that indomethacin or NS-398 delivery accelerated zebrafish death rates during LPS induced sepsis. When COX inhibitors were released over 30 days from an osmotic pump implant in mice, macrophages from peritoneal cavities and adipose tissue produced more TNFα in both the basal state and under LPS stimulation. Consequently, indomethacin-exposed mice showed accelerated systemic inflammation after LPS injection. Our findings suggest that macrophages exhibit a more inflammatory phenotype when COX activities are chronically inhibited.
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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.