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Impact of tobacco smoking on cytokine signaling via interleukin-17A in the peripheral airways

Authors Levänen B, Glader P, Dahlén B, Billing B, Qvarfordt I, Palmberg L, Larsson K, Lindén A

Received 1 March 2016

Accepted for publication 8 May 2016

Published 6 September 2016 Volume 2016:11(1) Pages 2109—2116

DOI https://doi.org/10.2147/COPD.S99900

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 4

Editor who approved publication: Dr Richard Russell


Bettina Levänen,1 Pernilla Glader,2 Barbro Dahlén,3,4 Bo Billing,4 Ingemar Qvarfordt,2 Lena Palmberg,1 Kjell Larsson,1 Anders Lindén1,2,4

1Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 2Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 3Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 4Lung Allergy Clinic, Karolinska University Hospital, Stockholm, Sweden


Abstract: There is excessive accumulation of neutrophils in the airways in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms remain poorly understood. It is known that extracellular cytokine signaling via interleukin (IL)-17A contributes to neutrophil accumulation in the airways but nothing is known about the impact of tobacco smoking on extracellular signaling via IL-17A. Here, we characterized the impact of tobacco smoking on extracellular cytokine signaling via IL-17A in the peripheral airways in long-term smokers with and without COPD and in occasional smokers before and after short-term exposure to tobacco smoke. We quantified concentrations of IL-17A protein in cell-free bronchoalveolar lavage (BAL) fluid samples (Immuno-quantitative PCR) and cytotoxic T-cells (immunoreactivity for CD8+ and CD3+) in bronchial biopsies. Matrix metalloproteinase-8 and human beta defensin 2 proteins were also quantified (enzyme-linked immunosorbent assay) in the BAL samples. The concentrations of IL-17A in BAL fluid were higher in long-term smokers without COPD compared with nonsmoking healthy controls, whereas those with COPD did not differ significantly from either of the other groups. Short-term exposure to tobacco smoke did not induce sustained alterations in these concentrations in occasional smokers. Long-term smokers displayed higher concentrations of IL-17A than did occasional smokers. Moreover, these concentrations correlated with CD8+ and CD3+ cells in biopsies among long-term smokers with COPD. In healthy nonsmokers, BAL concentrations of matrix metalloproteinase-8 and IL-17A correlated, whereas this was not the case in the pooled group of long-term smokers with and without COPD. In contrast, BAL concentrations of human beta defensin 2 and IL-17A correlated in all study groups. This study implies that long-term but not short-term exposure to tobacco smoke increases extracellular cytokine signaling via IL-17A in the peripheral airways. In the smokers with COPD, this signaling may involve cytotoxic T-cells. Long-term exposure to tobacco smoke leads to a disturbed association of extracellular IL-17A signaling and matrix metalloproteinase-8, of potential importance for the coordination of antibacterial activity.

Keywords: BAL, COPD, IL-17, tobacco, long-term smoking, occasional smoking

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