title: Elevated GDF-15 contributes to pulmonary inflammation upon cigarette smoke exposure.
abstract: The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-β superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-β superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice. Next, we exposed GDF-15 KO and control mice to air or CS and evaluated pulmonary inflammation. GDF-15 levels were higher in sputum supernatant and lung tissue of patients with COPD and smokers without COPD compared with never smokers. Immunohistochemistry revealed GDF-15 staining in the airway epithelium. Increased expression and secretion of GDF-15 was confirmed in vitro in CS-exposed pHBECs compared with air-exposed pHBECs. Similarly, GDF-15 levels were increased in lungs of CS-exposed mice. Importantly, GDF-15 deficiency attenuated the CS-induced pulmonary inflammation. These results suggest that increased GDF-15-as observed in lungs of smokers and patients with COPD-contributes to CS-induced pulmonary inflammation.
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: F M
authors.initials: FM
authors.lastname: Verhamme
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: L J M
authors.initials: LJM
authors.lastname: Seys
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: E G
authors.initials: EG
authors.lastname: De Smet
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Provoost
authors.affiliation: Respiratory Medicine, University Hospital Leuven, Department of Clinical and Experimental Medicine, KU Leuven, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Janssens
authors.affiliation: Unit for Molecular Immunology and Inflammation, Inflammation Research Center VIB Ghent University and Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Elewaut
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: G F
authors.initials: GF
authors.lastname: Joos
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: G G
authors.initials: GG
authors.lastname: Brusselle
authors.affiliation: Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: K R
authors.initials: KR
authors.lastname: Bracke
mesh_terms: D000368:Aged; D000818:Animals; D001980:Bronchi / Q000473:pathology; D002478:Cells, Cultured; D000073865:Cigarette Smoking / Q000009:adverse effects*; D015331:Cohort Studies; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15