Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD

Antonino Di Stefano, Gaetano Caramori, Adam Barczyk, Chiara Vicari, Paola Brun, Andrea Zanini, Francesco Cappello, Elvira Garofano, Anna Padovani, Marco Contoli, Paolo Casolari, Andrew L. Urham, Kian Fan Chung, Peter J. Barnes, Alberto Papi, Ian Adcock, Bruno Balbi

Research output: Contribution to journalArticle

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. Objectives 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 ? and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1ß 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-1ß 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.

Original languageEnglish
Pages (from-to)516-524
Number of pages9
JournalThorax
Volume69
Issue number6
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Di Stefano, A., Caramori, G., Barczyk, A., Vicari, C., Brun, P., Zanini, A., Cappello, F., Garofano, E., Padovani, A., Contoli, M., Casolari, P., Urham, A. L., Fan Chung, K., Barnes, P. J., Papi, A., Adcock, I., & Balbi, B. (2014). Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD. Thorax, 69(6), 516-524. https://doi.org/10.1136/thoraxjnl-2012-203062