title: The inflammasome pathway in stable COPD and acute exacerbations.
abstract: Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.
authors.affiliation: Fundació Clinic per a la Recerca Biomèdica, Barcelona, Spain; CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; These authors contributed equally to this work.
authors.forename: Rosa
authors.initials: R
authors.lastname: Faner
authors.affiliation: CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; Pulmonary Service, Hospital Txagorritxu, Vitoria, Spain; These authors contributed equally to this work.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sobradillo
authors.affiliation: CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; University Hospital Son Espases-IdISPa, Palma de Mallorca, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Noguera
authors.affiliation: University Hospital Son Espases-IdISPa, Palma de Mallorca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez
authors.affiliation: Fundació Clinic per a la Recerca Biomèdica, Barcelona, Spain; CIBER Respiratory Diseases (CIBERES), Barcelona, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Cruz
authors.affiliation: Fundació Clinic per a la Recerca Biomèdica, Barcelona, Spain; CIBER Respiratory Diseases (CIBERES), Barcelona, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: López-Giraldo
authors.affiliation: Institut Respiratori, Hospital Clinic, Barcelona, Spain; Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Eugeni
authors.initials: E
authors.lastname: Ballester
authors.affiliation: Institut Respiratori, Hospital Clinic, Barcelona, Spain; Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Nestor
authors.initials: N
authors.lastname: Soler
authors.affiliation: Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Immunology Dept, Hospital Clinic, Barcelona, Spain.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Arostegui
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERHED, Murcia's BioHealth, Research Institute IMIB-Arrixaca, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelegrín
authors.affiliation: CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; Institut Respiratori, Hospital Clinic, Barcelona, Spain; Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.affiliation: Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Immunology Dept, Hospital Clinic, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.affiliation: CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; University Hospital Son Espases-IdISPa, Palma de Mallorca, Spain.
authors.forename: Borja G
authors.initials: BG
authors.lastname: Cosio
authors.affiliation: Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Immunology Dept, Hospital Clinic, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Juan
authors.affiliation: Fundació Clinic per a la Recerca Biomèdica, Barcelona, Spain; CIBER Respiratory Diseases (CIBERES), Barcelona, Spain; Institut Respiratori, Hospital Clinic, Barcelona, Spain; Biomedic Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí