IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis
| العنوان: | IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis |
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| المؤلفون: | Vincenzo Nicola Talesa, Claudia Galosi, Vasilis Oikonomou, Vincenzina Lucidi, Cornelia Lass-Flörl, Charles A. Dinarello, Valerio Napolioni, Matteo Puccetti, Rossana G. Iannitti, Luigi Porcaro, Carla Colombo, Luigi Ratclif, Lisa Cariani, Luigina Romani, Maria Chiara Russo, Cristina Massi-Benedetti, Monica Borghi, Antonella De Luca, Gabriella Ricciotti, Frank L. van de Veerdonk, Fabio Majo, Ersilia Fiscarelli, Helmut Ellemunter, Marilena Pariano, Fernando Maria de Benedictis |
| المصدر: | Nature Communications Nature Communications, 7, 10791 Nature Communications, 7, pp. 10791 Nature Communications, Vol 7, Iss 1, Pp 1-16 (2016) |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cystic Fibrosis, Inflammasomes, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], General Physics and Astronomy, Cystic Fibrosis Transmembrane Conductance Regulator, Fluorescent Antibody Technique, Cystic fibrosis, Mice, 0302 clinical medicine, NLRC4, Child, Lung, Mice, Knockout, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Inflammasome, respiratory system, Middle Aged, Receptor antagonist, Immunohistochemistry, Cystic fibrosis transmembrane conductance regulator, 3. Good health, Child, Preschool, Pseudomonas aeruginosa, Cytokines, Female, medicine.symptom, medicine.drug, Adult, Adolescent, medicine.drug_class, Science, Blotting, Western, Inflammation, Enzyme-Linked Immunosorbent Assay, Respiratory Mucosa, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, Young Adult, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Autophagy, In Situ Nick-End Labeling, Animals, Aspergillosis, Humans, Pseudomonas Infections, Anakinra, Aspergillus fumigatus, Macrophages, Calcium-Binding Proteins, Infant, Epithelial Cells, General Chemistry, medicine.disease, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, Disease Models, Animal, Interleukin 1 Receptor Antagonist Protein, 030104 developmental biology, Immunology, biology.protein, Apoptosis Regulatory Proteins, Carrier Proteins, 030215 immunology |
| الوصف: | Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF. IL-1-mediated inflammation contributes to the pathogenesis of cystic fibrosis. Here the authors show that this is largely due to NLRP3 activation, whereas NLRP4 induces IL-1Ra, limiting the overall inflammasome activity and providing a therapeutic angle to ameliorate the disease. |
| وصف الملف: | application/pdf |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4160f15fa7e4c0a401b355a495e56e9Test https://pubmed.ncbi.nlm.nih.gov/26972847Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b4160f15fa7e4c0a401b355a495e56e9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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