title: Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD.
abstract: BACKGROUND
  In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.
  
  
  OBJECTIVE
  To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.
  
  
  METHODS
  Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.
  
  
  RESULTS
  In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.
  
  
  CONCLUSIONS
  Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.
authors.affiliation: Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) e Tradate, Pavia, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Stefano
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.affiliation: Katedra i Klinika Pneumonologii Slaskiego Uniwersytetu Medycznego w Katowicach, Slaskiego, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Barczyk
authors.affiliation: Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) e Tradate, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vicari
authors.affiliation: Department of Molecular Medicine, Histology Unit, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) e Tradate, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanini
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Anatomia Umana, Università di Palermo, Palermo, Italy Istituto Euro-Mediterraneo di Scienza e Tecnologia, Palermo, Italy Istituto Paolo Sotgiu, Libera Università degli Studi di Scienze Umane e Tecnologiche, Lugano, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Garofano
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Contoli
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Casolari
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Durham
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.affiliation: Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) e Tradate, Pavia, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Balbi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000368:Aged; D001980:Bronchi / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis; D016022:Case-Control Studies; D050822:Cytokine Receptor gp130 / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D058847:Inflammasomes / Q000032:analysis* / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007378:Interleukins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000032:analysis; D012907:Smoking / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016207:Cytokines; D024243:HMGB1 Protein; C079241:IL1RL1 protein, human; D058847:Inflammasomes; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C502448:NLRP7 protein, human; D011956:Receptors, Cell Surface; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050822:Cytokine Receptor gp130; D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin
keywords: COPD Pathology; Innate Immunity