دورية أكاديمية
3-Hydroxy kynurenine treatment controls T. cruzi replication and the inflammatory pathology preventing the clinical symptoms of chronic Chagas disease.
العنوان: | 3-Hydroxy kynurenine treatment controls T. cruzi replication and the inflammatory pathology preventing the clinical symptoms of chronic Chagas disease. |
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المؤلفون: | Knubel CP; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina., Martínez FF, Acosta Rodríguez EV, Altamirano A, Rivarola HW, Diaz Luján C, Fretes RE, Cervi L, Motrán CC |
المصدر: | PloS one [PLoS One] 2011; Vol. 6 (10), pp. e26550. Date of Electronic Publication: 2011 Oct 19. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
مواضيع طبية MeSH: | Chagas Disease/*prevention & control , Kynurenine/*analogs & derivatives , Trypanosoma cruzi/*drug effects , Trypanosoma cruzi/*physiology, Animals ; Chagas Disease/immunology ; Chagas Disease/parasitology ; Chronic Disease ; Female ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/parasitology ; Interferon-gamma/metabolism ; Kynurenine/pharmacology ; Kynurenine/therapeutic use ; Mice ; Mice, Inbred BALB C ; Species Specificity ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/parasitology ; Trypanosoma cruzi/immunology ; Trypanosoma cruzi/pathogenicity |
مستخلص: | Background: 3-Hydroxy Kynurenine (3-HK) administration during the acute phase of Trypanosoma. cruzi infection decreases the parasitemia of lethally infected mice and improves their survival. However, due to the fact that the treatment with 3-HK is unable to eradicate the parasite, together with the known proapoptotic and immunoregulatory properties of 3-HK and their downstream catabolites, it is possible that the 3-HK treatment is effective during the acute phase of the infection by controlling the parasite replication, but at the same time suppressed the protective T cell response before pathogen clearance worsening the chronic phase of the infection. Therefore, in the present study, we investigated the effect of 3-HK treatment on the development of chronic Chagas' disease. Principal Findings: In the present study, we treated mice infected with T. cruzi with 3-HK at day five post infection during 5 consecutive days and investigated the effect of this treatment on the development of chronic Chagas disease. Cardiac functional (electrocardiogram) and histopathological studies were done at 60 dpi. 3-HK treatment markedly reduced the incidence and the severity of the electrocardiogram alterations and the inflammatory infiltrates and fibrosis in heart and skeletal muscle. 3-HK treatment modulated the immune response at the acute phase of the infection impairing the Th1- and Th2-type specific response and inducing TGF-β-secreting cells promoting the emergence of regulatory T cells and long-term specific IFN-γ secreting cells. 3-HK in vitro induced regulatory phenotype in T cells from T. cruzi acutely infected mice. Conclusions: Our results show that the early 3-HK treatment was effective in reducing the cardiac lesions as well as altering the pattern of the immune response in experimental Chagas' disease. Thus, we propose 3-HK as a novel therapeutic treatment able to control both the parasite replication and the inflammatory response. |
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المشرفين على المادة: | 27723548JL (3-hydroxykynurenine) 343-65-7 (Kynurenine) 82115-62-6 (Interferon-gamma) |
تواريخ الأحداث: | Date Created: 20111027 Date Completed: 20120224 Latest Revision: 20211020 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC3197528 |
DOI: | 10.1371/journal.pone.0026550 |
PMID: | 22028903 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1932-6203 |
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DOI: | 10.1371/journal.pone.0026550 |