title: Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema.
abstract: Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A(-/-)) exposed to CS compared with wild-type (WT) mice, IL-17A(-/-) mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A(-/-) mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A(-/-) mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A(-/-) mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A(-/-) mice and in CS-exposed WT and IL-17A(-/-) mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Meike
authors.initials: M
authors.lastname: Voss
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Lisa
authors.initials: L
authors.lastname: Wolf
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Kamyschnikow
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Bodo
authors.initials: B
authors.lastname: Wonnenberg
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Anja
authors.initials: A
authors.lastname: Honecker
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Lepper
authors.affiliation: Division of Asthma Mouse Models, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, Borstel, Germany; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Wegmann
authors.affiliation: Institute for Clinical and Experimental Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany;
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg/Saar, Germany; christoph.beisswenger@uks.eu.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beisswenger
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005541:Forced Expiratory Volume; D006706:Homeostasis; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*
chemical_list: D016207:Cytokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger
keywords: IL-17A; cigarette smoke; emphysema; lung damage; pulmonary function