The absence of functional PI3Kgamma prevents leukocyte recruitment and ameliorates DSS-induced colitis in mice
| العنوان: | The absence of functional PI3Kgamma prevents leukocyte recruitment and ameliorates DSS-induced colitis in mice |
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| المؤلفون: | Fiebo J.W. ten Kate, James C. H. Hardwick, Anje A. te Velde, Stefano Marengo, Elisa Ciraolo, Gijs R. van den Brink, Guy E. Boeckxstaens, Irene Franco, Daan W. Hommes, Emilio Hirsch, Willemijn A. van Dop |
| المساهمون: | Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Cancer Center Amsterdam, Pathology |
| المصدر: | Immunology Letters, 131(1), 33-39 Immunology letters, 131(1), 33-39. Elsevier |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Leukocyte migration, Colon, medicine.medical_treatment, Immunology, Inflammation, Inflammatory bowel disease, Severity of Illness Index, Mice, Intestinal mucosa, medicine, Leukocytes, Immunology and Allergy, Animals, Class Ib Phosphatidylinositol 3-Kinase, Humans, Colitis, Mice, Knockout, Lamina propria, Mucous Membrane, business.industry, Dextran Sulfate, medicine.disease, Mucosal immunology, Cytokines, Mice, Inbred C57BL, Disease Models, Animal, medicine.anatomical_structure, Cytokine, Mucosal immunology Leukocyte migration Cytokines Colitis active crohns-disease relapsing multiple-sclerosis inflammatory-bowel-disease placebo-controlled trial il-12 production interleukin-12 production rheumatoid-arthritis cytokine production oral fingolimod dependent role, Mutation, Tumor necrosis factor alpha, medicine.symptom, business |
| الوصف: | Phosphatidylinositol-3-kinase gamma (PI3K gamma) is the major PI3K that is activated in response to chemoattractants. It is responsible for the migration of leukocytes from the bloodstream to sites of injury or infection. Constant migration of new leukocytes to the intestinal mucosa may be an important factor in maintenance of inflammation and tissue damage in inflammatory bowel disease (IBD). Reducing this influx, for example by inhibition of PI3K gamma, might therefore be a potential goal for therapy. Here we investigated the role of PI3K gamma in the migration of leukocytes to sites of intestinal inflammation. We induced colitis in mice with a point mutation that inactivates PI3K gamma enzymatic activity ('kinase-dead') by oral administration of dextran sodium sulphate (DSS). Mice were treated with 1.5% DSS for 1 week and effects on cytokine production, leukocyte recruitment and disease severity were examined. Both clinical and histological parameters showed that the severity of colitis was significantly reduced in PI3K gamma-kinase-dead mice compared to controls. Although mutant mice had a less severe colitis than controls they produced significantly more pro-inflammatory Th1 cytokines such as Il-12. Tnf alpha and Ifn gamma and more Il-10. PI3K gamma mutant mice showed increased numbers of resident macrophages and T cells in the colonic lamina propria in an unstressed condition but failed to recruit new leukocytes to the mucosa upon treatment with DSS despite the increased cytokine levels. These results suggest that PI3K gamma plays a critical role in lamina propria leukocyte trafficking and that loss of PI3Ky-activity ameliorates DSS-induced colitis in mice. (C) 2010 Elsevier B.V. All rights reserved. |
| تدمد: | 1879-0542 0165-2478 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b54a444661f46a03c72c00890e2289bTest https://pubmed.ncbi.nlm.nih.gov/20347874Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....7b54a444661f46a03c72c00890e2289b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18790542 01652478 |
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