title: Cigarette smoke affects IL-17A, IL-17F and IL-17 receptor expression in the lung tissue: Ex vivo and in vitro studies.
abstract: Cigarette smoke is a risk factor for Chronic Obstructive Pulmonary Disease (COPD). Th-17 cytokines are involved in the pathogenesis of COPD. We aimed to evaluate the role of cigarette smoke on the expression of IL-17A, IL-17F and IL-17R in airways of COPD patients. Epithelial and subepithelial immunoreactivity for IL-17A, IL-17F and IL-17R was assessed in surgical specimens from COPD patients (n=15) and from healthy subjects (HC) (n=10) by immunohistochemistry. In vitro, human epithelial cell line 16HBE and A549 as well as PBMC from normal donors were stimulated with cigarette smoke extract (CSE) (0%, 2.5%, 5%, 10%) to evaluate the IL-17A, IL-17F and IL-17R expression by flow cytometry. Furthermore, rhIL-17A and CSE stimulation was evaluated on proliferation and apoptosis in 16HBE and in A549. In central and distal airways immunoreactivity for IL-17A, IL-17F and IL-17R significantly increased in the epithelium and IL-17A in the subepithelium from COPD than in HC. In distal airway, immunoreactivity for IL-17F increased in the subepithelium of COPD than in HC. IL-17A immunoreactivity positively correlate with IL-17R and total pack years in the epithelium from central and distal airways of COPD patients. In vitro, CSE stimulation significantly increased IL-17F and IL-17R in 16HBE (2.5%) and A549 (5%) while IL-17A and IL-17F in PBMC (10%). IL-17A and CSE stimulation, rather than CSE or rhIL-17A alone, significantly increased proliferation in 16HBE and apoptosis in A549. Cigarette smoke increases Th17 immunity in lung tissue of COPD patients, promoting the mechanism of proliferation and apoptosis in airway epithelial cells.
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Riccobono
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chiappara
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Sano
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Anzalone
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Gagliardo
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
authors.forename: Fabio L M
authors.initials: FLM
authors.lastname: Ricciardolo
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sorbello
authors.affiliation: Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Pipitone
authors.affiliation: Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Vitulo
authors.affiliation: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy. Electronic address: profita@ibim.cnr.it.
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D012906:Smoke; D014026:Nicotiana
chemical_list: C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D012906:Smoke
keywords: Airway inflammation; COPD; Epithelial cells; Th17 immunity