Title |
IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis
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Published in |
Nature Communications, March 2016
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DOI | 10.1038/ncomms10791 |
Pubmed ID | |
Authors |
Rossana G. Iannitti, Valerio Napolioni, Vasilis Oikonomou, Antonella De Luca, Claudia Galosi, Marilena Pariano, Cristina Massi-Benedetti, Monica Borghi, Matteo Puccetti, Vincenzina Lucidi, Carla Colombo, Ersilia Fiscarelli, Cornelia Lass-Flörl, Fabio Majo, Lisa Cariani, Maria Russo, Luigi Porcaro, Gabriella Ricciotti, Helmut Ellemunter, Luigi Ratclif, Fernando Maria De Benedictis, Vincenzo Nicola Talesa, Charles A. Dinarello, Frank L. van de Veerdonk, Luigina Romani |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 33% |
United Kingdom | 1 | 17% |
Unknown | 3 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 50% |
Scientists | 2 | 33% |
Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Australia | 1 | <1% |
Unknown | 180 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 35 | 19% |
Researcher | 31 | 17% |
Student > Master | 17 | 9% |
Student > Bachelor | 12 | 7% |
Student > Doctoral Student | 10 | 5% |
Other | 31 | 17% |
Unknown | 46 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 26 | 14% |
Medicine and Dentistry | 26 | 14% |
Immunology and Microbiology | 25 | 14% |
Biochemistry, Genetics and Molecular Biology | 20 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 4% |
Other | 24 | 13% |
Unknown | 53 | 29% |