title: Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD.
abstract: Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial-mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts.We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial-fibroblast interaction in COPD.
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands University of British Columbia, Centre for Heart Lung Innovation, Dept of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada Emmanuel.osei@hli.ubc.ca.
authors.forename: Emmanuel T
authors.initials: ET
authors.lastname: Osei
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Dept of Pulmonology, Groningen, The Netherlands.
authors.forename: Jacobien A
authors.initials: JA
authors.lastname: Noordhoek
authors.affiliation: University of British Columbia, Centre for Heart Lung Innovation, Dept of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada.
authors.forename: Tillie L
authors.initials: TL
authors.lastname: Hackett
authors.affiliation: University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands University of Groningen, Dept of Molecular Pharmacology, Groningen, The Netherlands.
authors.forename: Anita I R
authors.initials: AI
authors.lastname: Spanjer
authors.affiliation: University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Dept of Pulmonology, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands These two authors contributed equally to this work.
authors.forename: Corry-Anke
authors.initials: CA
authors.lastname: Brandsma
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Dept of Pulmonology, Groningen, The Netherlands These two authors contributed equally to this work.
authors.forename: Irene H
authors.initials: IH
authors.lastname: Heijink
mesh_terms: D001980:Bronchi / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D053582:Interleukin-1alpha / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012906:Smoke; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana
chemical_list: C508606:CXCL8 protein, human; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D016209:Interleukin-8; D012906:Smoke