title: Cigarette smoke alters the secretome of lung epithelial cells.
abstract: Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease.
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mossina
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lukas
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.affiliation: Department of Medicine, Vermont Lung Center (VLC), University of Vermont, Burlington, VT, USA.
authors.forename: Franziska E
authors.initials: FE
authors.lastname: Uhl
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mutze
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schamberger
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Staab-Weijnitz
authors.affiliation: Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research (DZL), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.affiliation: Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research (DZL), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Königshoff
authors.affiliation: Research Unit Protein Science, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.|Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research (DZL), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Comprehensive, Pneumology Center (CPC), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), University Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Meiners
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D040901:Proteomics / Q000379:methods; D012907:Smoking / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects
keywords: Biomedicine; Cigarette smoke; Lung; Proteomic profiling; Secretome