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

Abstract

BackgroundIn 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.ObjectivesTo 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.MethodsInnate 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.ResultsIn 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.ConclusionsIncreased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.

Phospho-p38 MAPK Expression in COPD Patients and Asthmatics and in Challenged Bronchial Epithelium

“…These data, obtained from stable COPD patients by immunohistochemistry, confirm previously reported higher numbers of neutrophils and CD8+ cells in severe/very severe COPD (Table 4) [28].…”

Regulation and Function of the Nucleotide Binding Domain Leucine-Rich Repeat-Containing Receptor, Pyrin Domain-Containing-3 Inflammasome in Lung Disease

“…This study reported lack of NLRP3 inflammasome activation in COPD, with no differences in caspase-1 activation, IL-1b, or IL-18 levels in bronchial biopsies or in BAL between the groups (46). It remains conceivable of a role of the inflammasome system in toxic reactions to CS exposure, as well as a component of immune reactions during secondary infections associated with COPD.…”

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

“…Moreover, NLRP3 inflammasome activation has been linked to neutrophilic asthma [19], while inflammasome-regulated cytokines are critical mediators of acute lung injury [20]. Alternatively, a recent report suggests that the NLRP3 inflammasome pathway is not linked to the severity of stable chronic obstructive pulmonary disease following analyses in the bronchoalveolar lavage fluid (BALF) and cellular components [21]. Recent evidence showing a possible activation of NLRP3 by cigarette smoking, another environmental risk factor for both IPF and rheumatoid arthritis, further supports the possible implication of inflammasomes in lung fibrosis [10,18].…”