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- Title
IL-36 Cytokines Promote Inflammation in the Lungs of Long-Term Smokers.
- Authors
Kovach, Melissa A.; Karlhans Che; Brundin, Bettina; Andersson, Anders; Asgeirsdottir, Helga; Padra, Médea; Lindén, Sara K.; Qvarfordt, Ingemar; Newstead, Michael W.; Standiford, Theodore J.; Lindén, Anders
- Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease with high morbidity and mortality. The IL-36 family are proinflammatory cytokines that are known to shape innate immune responses, including those critical to bacterial pneumonia. The objective of this study was to determine whether IL-36 cytokines promote a proinflammatory milieu in the lungs of longterm smokers with and without COPD. Concentrations of IL-36 cytokines were measured in plasma and BAL fluid from subjects in a pilot study (n = 23) of long-term smokers with and without COPD in vivo and from a variety of lung cells (from 3-5 donors) stimulated with bacteria or cigarette smoke components in vitro. Pulmonary macrophages were stimulated with IL-36 cytokines in vitro, and chemokine and cytokine production was assessed. IL-36aand IL-36g are produced to varying degrees in murine and human lung cells in response to bacterial stimuli and cigarette smoke components in vitro. Moreover, whereas IL-36g production is upregulated early after cigarette smoke stimulation and wanes over time, IL-36a production requires a longer duration of exposure. IL-36a and IL-36g are enhanced systemically and locally in long-term smokers with and without COPD, and local IL-36a concentrations display a positive correlation with declining ventilatory lung function and increasing proinflammatory cytokine concentrations. In vitro, IL-36a and IL-36g induce proinflammatory chemokines and cytokines in a concentration-dependent fashion that requires IL-36R and MyD88. IL-36 cytokine production is altered in long-term smokers with and without COPD and contributes to shaping a proinflammatory milieu in the lungs.
- Subjects
OBSTRUCTIVE lung disease treatment; OBSTRUCTIVE lung disease diagnosis; PNEUMONIA-related mortality; RISK factors of pneumonia; MACROPHAGES
- Publication
American Journal of Respiratory Cell & Molecular Biology, 2021, Vol 64, Issue 2, p173
- ISSN
1044-1549
- Publication type
Article
- DOI
10.1165/rcmb.2020-0035OC