IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

Rossana Iannitti; V. Napolioni; Vasilis Oikonomou; Antonella De Luca; Claudia Galosi; Marilena Pariano; Cristina Massi-Benedetti; Monica Borghi; Matteo Puccetti; Vincenzina Lucidi; Carla Colombo; Ersilia Vita Fiscarelli; C. Lass-Flörl; Fabio Majo; Lisa Cariani; Maria Chiara Russo; Luigi Porcaro; G. Ricciotti; Helmut Ellemunter; Luigi Ratclif; Fernando Maria De Benedictis; Vincenzo N. Talesa; Charles Anthony Dinarello; Frank Van De Veerdonk; Luigina Romani

doi:10.1038/ncomms10791

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

Rossana Iannitti, V. Napolioni, Vasilis Oikonomou, Antonella De Luca, Claudia Galosi, Marilena Pariano, Cristina Massi-Benedetti, Monica Borghi, Matteo Puccetti, Vincenzina Lucidi, Carla Colombo, Ersilia Vita Fiscarelli, C. Lass-Flörl, Fabio Majo, Lisa Cariani, Maria Chiara Russo, Luigi Porcaro, G. Ricciotti, Helmut Ellemunter, Luigi RatclifFernando Maria De Benedictis, Vincenzo N. Talesa, Charles Anthony Dinarello, Frank Van De Veerdonk, Luigina Romani

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	10791
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10791
Publication status	Published - Mar 14 2016

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Chemistry(all)
Physics and Astronomy(all)

Access to Document

10.1038/ncomms10791

Cite this

Iannitti, R., Napolioni, V., Oikonomou, V., De Luca, A., Galosi, C., Pariano, M., Massi-Benedetti, C., Borghi, M., Puccetti, M., Lucidi, V., Colombo, C., Fiscarelli, E. V., Lass-Flörl, C., Majo, F., Cariani, L., Russo, M. C., Porcaro, L., Ricciotti, G., Ellemunter, H., ... Romani, L. (2016). IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis. Nature Communications, 7, [10791]. https://doi.org/10.1038/ncomms10791

Iannitti, R, Napolioni, V, Oikonomou, V, De Luca, A, Galosi, C, Pariano, M, Massi-Benedetti, C, Borghi, M, Puccetti, M, Lucidi, V, Colombo, C, Fiscarelli, EV, Lass-Flörl, C, Majo, F , Cariani, L , Russo, MC, Porcaro, L, Ricciotti, G, Ellemunter, H, Ratclif, L, De Benedictis, FM, Talesa, VN, Dinarello, CA, Van De Veerdonk, F & Romani, L 2016, 'IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis', Nature Communications, vol. 7, 10791. https://doi.org/10.1038/ncomms10791

@article{b8b4714cd1da4490a43649023bed5dde,

title = "IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis",

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.",

author = "Rossana Iannitti and V. Napolioni and Vasilis Oikonomou and {De Luca}, Antonella and Claudia Galosi and Marilena Pariano and Cristina Massi-Benedetti and Monica Borghi and Matteo Puccetti and Vincenzina Lucidi and Carla Colombo and Fiscarelli, {Ersilia Vita} and C. Lass-Fl{\"o}rl and Fabio Majo and Lisa Cariani and Russo, {Maria Chiara} and Luigi Porcaro and G. Ricciotti and Helmut Ellemunter and Luigi Ratclif and {De Benedictis}, {Fernando Maria} and Talesa, {Vincenzo N.} and Dinarello, {Charles Anthony} and {Van De Veerdonk}, Frank and Luigina Romani",

year = "2016",

month = mar,

day = "14",

doi = "10.1038/ncomms10791",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "NLM (Medline)",

}

TY - JOUR

T1 - IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

AU - Iannitti, Rossana

AU - Napolioni, V.

AU - Oikonomou, Vasilis

AU - De Luca, Antonella

AU - Galosi, Claudia

AU - Pariano, Marilena

AU - Massi-Benedetti, Cristina

AU - Borghi, Monica

AU - Puccetti, Matteo

AU - Lucidi, Vincenzina

AU - Colombo, Carla

AU - Fiscarelli, Ersilia Vita

AU - Lass-Flörl, C.

AU - Majo, Fabio

AU - Cariani, Lisa

AU - Russo, Maria Chiara

AU - Porcaro, Luigi

AU - Ricciotti, G.

AU - Ellemunter, Helmut

AU - Ratclif, Luigi

AU - De Benedictis, Fernando Maria

AU - Talesa, Vincenzo N.

AU - Dinarello, Charles Anthony

AU - Van De Veerdonk, Frank

AU - Romani, Luigina

PY - 2016/3/14

Y1 - 2016/3/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84961827538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961827538&partnerID=8YFLogxK

U2 - 10.1038/ncomms10791

DO - 10.1038/ncomms10791

M3 - Article

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10791

ER -

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this