ArticleBritish journal of pharmacology2006
A small molecule, orally active, alpha4beta1/alpha4beta7 dual antagonist reduces leukocyte infiltration and airway hyper-responsiveness in an experimental model of allergic asthma in Brown Norway rats.
Article in British journal of pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 32 citations in OpenAlex.
- Integrin α4β7: Pathogenic Roles in Metabolic and Inflammatory Diseases and Translational Therapeutics.Journal of inflammation research · 2026Review
- The Role and Application of MAdCAM-1/α4β7-Induced Lymphocyte Migration in Inflammatory Enterohepatic Diseases.Biomedicines · 2025Review
- The integrin receptor betaRespiratory research · 2024Article
- Microneedle-Mediated Immunization Promotes Lung CD8+ T-Cell Immunity.The Journal of investigative dermatology · 2023Article
- Article
- Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Smad7 in intestinal CD4Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- DS-70, a novel and potent αBritish journal of pharmacology · 2018Article
- Integrins are Mechanosensors That Modulate Human Eosinophil Activation.Frontiers in immunology · 2015Article
- Integrins as Therapeutic Targets for Respiratory Diseases.Current molecular medicine · 2015Review
- Effect of low-level laser therapy on allergic asthma in rats.Lasers in medical science · 2014Article
- Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.Chemical Society reviews · 2012Review
- Therapeutic targeting of eosinophil adhesion and accumulation in allergic conjunctivitis.Frontiers in pharmacology · 2012Article
- Shining a light on intestinal traffic.Clinical & developmental immunology · 2012Review
- Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation.Journal of leukocyte biology · 2010Article
- An alpha4beta1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice.European journal of pharmacology · 2009Article
- Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma.Journal of leukocyte biology · 2008Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
alpha(4)beta(1) and alpha(4)beta(7) integrins are preferentially expressed on eosinophils and mononuclear leukocytes and play critical roles in their recruitment to inflammatory sites. We investigated the effects of TR14035, a small molecule, alpha(4)beta(1)/alpha(4)beta(7) dual antagonist, in a rat model of allergic asthma. Actively sensitized rats were challenged with aerosol antigen or saline on day 21, and the responses evaluated 24 and 48-h later. TR14035 (3 mg kg(-1), p.o.) was given 1-h before and 4-h after antigen or saline challenge. Airway hyper-responsiveness to intravenous 5-hydroxytryptamine was suppressed in TR14035-treated rats. Eosinophil, mononuclear cell and neutrophil counts, and eosinophil peroxidase and protein content in the bronchoalveolar lavage fluid (BALF) were decreased in TR14035-treated rats. Histological study showed a marked reduction of lung inflammatory lesions by TR14035. At 24-h postchallenge, antigen-induced lung interleukin (IL)-5 mRNA upregulation was suppressed in TR14035-treated rats. By contrast, IL-4 levels in BALF were not significantly affected by TR14035 treatment. IL-4 selectively upregulates vascular cell adhesion molecule-1 (VCAM-1), which is the main endothelial ligand of alpha(4) integrins. Intravital microscopy within the rat mesenteric microcirculation showed that 24-h exposure to 1 microg per rat of IL-4 induced a significant increase in leukocyte rolling flux, adhesion and emigration. These responses were decreased by 48, 100 and 99%, respectively in animals treated with TR14035. In conclusion, TR14035, by acting on alpha(4)beta(1) and alpha(4)beta(7) integrins, is an orally active inhibitor of airway leukocyte recruitment and hyper-responsiveness in animal models with potential interest for the treatment of asthma.
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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.