ArticleProceedings of the National Academy of Sciences of the United States of America2004
A beta-oxidation-resistant lipoxin A4 analog treats hapten-induced colitis by attenuating inflammation and immune dysfunction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 57 papers.
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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.
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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
57 citing papers in PubMed, 145 citations in OpenAlex.
- Reprogramming Inflammatory Macrophages with Specialized Pro-Resolving Lipid Mediators: A Novel Immunotherapeutic Strategy for Asthma.Biomedicines · 2026Review
- Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35.British journal of pharmacology · 2022Review
- MicroRNAs in shaping the resolution phase of inflammation.Seminars in cell & developmental biology · 2022Review
- Involvement of Proinflammatory Arachidonic Acid (ARA) Derivatives in Crohn's Disease (CD) and Ulcerative Colitis (UC).Journal of clinical medicine · 2022Article
- Interrelationship between the 5-lipoxygenase pathway and microbial dysbiosis in the progression of Alzheimer's disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation.International journal of molecular sciences · 2021Review
- Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing.Inflammatory bowel diseases · 2020Review
- Therapeutic Potential of Lipoxin AACS pharmacology & translational science · 2020Review
- Resolution of ulcerative colitis.Seminars in immunopathology · 2019Review
- Endogenous Specialized Proresolving Mediator Profiles in a Novel Experimental Model of Lymphatic Obstruction and Intestinal Inflammation in African Green Monkeys.The American journal of pathology · 2019Article
- Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD.Nature reviews. Gastroenterology & hepatology · 2019Review
- Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model.The Journal of clinical investigation · 2019Article
- Eicosanoids in the gastrointestinal tract.British journal of pharmacology · 2019Review
- A Quantitative Analysis of Colonic Mucosal Oxylipins and Endocannabinoids in Treatment-Naïve and Deep Remission Ulcerative Colitis Patients and the Potential Link With Cytokine Gene Expression.Inflammatory bowel diseases · 2019Article
- Omega-3 Polyunsaturated Fatty Acids and Their Bioactive Metabolites in Gastrointestinal Malignancies Related to Unresolved Inflammation. A Review.Frontiers in pharmacology · 2019Review
- Production of lipid mediators across different disease stages of dextran sodium sulfate-induced colitis in mice.Journal of lipid research · 2018Article
- Can inflammation be resolved in Alzheimer's disease?Therapeutic advances in neurological disorders · 2018Review
- Neutrophils as protagonists and targets in chronic inflammation.Nature reviews. Immunology · 2017Review
- Actors and Factors in the Resolution of Intestinal Inflammation: Lipid Mediators As a New Approach to Therapy in Inflammatory Bowel Diseases.Frontiers in immunology · 2017Review
- The Dual Role of Neutrophils in Inflammatory Bowel Diseases.Journal of clinical medicine · 2016Review
Corrections and comments
- Expression of concern
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipoxins and aspirin-triggered 15-epi-lipoxins (ATL) are counter-regulatory eicosanoids with potent antiinflammatory actions. Oral efficacy and mechanism of action of ZK-192, a beta-oxidation-resistant 3-oxa-ATL analog, were examined in trinitrobenzenesulphonate (TNBS)-induced colitis. When dosed orally once daily, 300 and 1,000 mug/kg ZK-192 markedly attenuated TNBS colitis in rodents both in preventive and therapeutic regimens. ZK-192 attenuated weight loss, macroscopic and histologic colon injury, mucosal neutrophil infiltration, and colon wall thickening. ZK-192 was as effective as 3-10 mg/kg oral prednisolone. ZK-192 decreased mucosal mRNA levels for several inflammatory mediators: inducible nitric oxide synthase, cyclooxygenase 2, and macrophage inflammatory protein 2. ZK-192 also decreased mucosal mRNA and protein levels of T helper 1 effector cytokines: tumor necrosis factor alpha, IL-2, and IFN-gamma. Systemic levels of these cytokines were also dramatically attenuated. CD3/CD28-mediated costimulation of T helper 1 effector cytokine release in lamina propria mononuclear cells was markedly inhibited by ZK-192 ex vivo and in vitro. ZK-192 also prevented colitis in lymphocyte-deficient severe combined immunodeficient mice, with approximately 75% inhibition of mucosal tumor necrosis factor alpha and IL-2 levels. The results are further evidence that innate immune cells function as triggers for hapten-induced colitis. The combined antiinflammatory and immunomodulatory effects of ZK-192 in TNBS colitis suggest that ATL analogs may be an attractive oral treatment approach for inflammatory bowel diseases.
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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.