The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of Irinotecan-Induced Intestinal Mucositis
| العنوان: | The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of Irinotecan-Induced Intestinal Mucositis |
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| المؤلفون: | Fernando Q. Cunha, Rangel L. Silva, Deysi Viviana Tenazoa Wong, Vanessa F. Borges, Gabriela Loiola Ponte Batista, Cibele Barreto Mano de Carvalho, Carlos W. S. Wanderley, Maraiza Alves Teixeira, Amanda X. Couto Bem, Gerly Anne de Castro Brito, Ronaldo A. Ribeiro, Paulo Roberto Carvalho Almeida, Roberto C. P. Lima-Júnior, Thiago M. Cunha, Caio Abner Leite |
| المصدر: | PLoS ONE PLoS ONE, Vol 10, Iss 10, p e0139985 (2015) Repositório Institucional da Universidade Federal do Ceará (UFC) Universidade Federal do Ceará (UFC) instacron:UFC Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| بيانات النشر: | Public Library of Science, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Diarrhea, Mucositis, lcsh:Medicine, Ileum, Inflammation, Bacteremia, Biology, Pharmacology, Irinotecan, Pathogenesis, Mice, medicine, Animals, Diarreia, Intestinal Mucosa, Receptor, lcsh:Science, Peroxidase, Mice, Knockout, Mucosite, Multidisciplinary, lcsh:R, hemic and immune systems, PROTEÍNAS, medicine.disease, Toll-Like Receptor 2, TLR2, Intestinal Diseases, medicine.anatomical_structure, Myeloperoxidase, Toll-Like Receptor 9, Immunology, Myeloid Differentiation Factor 88, biology.protein, lcsh:Q, Camptothecin, medicine.symptom, medicine.drug, Research Article, Signal Transduction |
| الوصف: | Intestinal mucositis is a common side effect of irinotecan-based anticancer regimens. Mucositis causes cell damage, bacterial/endotoxin translocation and production of cytokines including IL–1 and IL–18. These molecules and toll-like receptors (TLRs) activate a common signaling pathway that involves the Myeloid Differentiation adaptor protein, MyD88, whose role in intestinal mucositis is unknown. Then, we evaluated the involvement of TLRs and MyD88 in the pathogenesis of irinotecan-induced intestinal mucositis. MyD88-, TLR2- or TLR9-knockout mice and C57BL/6 (WT) mice were given either saline or irinotecan (75 mg/kg, i.p. for 4 days). On day 7, animal survival, diarrhea and bacteremia were assessed, and following euthanasia, samples of the ileum were obtained for morphometric analysis, myeloperoxidase (MPO) assay and measurement of pro-inflammatory markers. Irinotecan reduced the animal survival (50%) and induced a pronounced diarrhea, increased bacteremia, neutrophil accumulation in the intestinal tissue, intestinal damage and more than twofold increased expression of MyD88 (200%), TLR9 (400%), TRAF6 (236%), IL–1β (405%), IL–18 (365%), COX–2 (2,777%) and NF-κB (245%) in the WT animals when compared with saline-injected group (P |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c38bf8bb2f8ac720e72bed5da4ddd72fTest http://europepmc.org/articles/PMC4595146Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c38bf8bb2f8ac720e72bed5da4ddd72f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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