title: Cigarette smoke alters IL-33 expression and release in airway epithelial cells.
abstract: Airway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored. Mini-BALs, but not sera, from smokers show reduced concentrations of IL-33. The expression of IL-33 was increased also in bronchial epithelium from smokers. 20% CSE reduced IL-33 release but increased the mRNA for IL-33 by real time PCR and the intracellular expression of IL-33 in bronchial epithelial cells as confirmed by flow cytometry, immunocytochemistry and western blot analysis. The effect of CSE on IL-33 expression was also observed in primary bronchial epithelial cells. IL-33 expression was mainly concentrated within the cytoplasm of the cells. LPS, an agonist of TLR4, reduced IL-33 expression, and an inhibitor of TLR4 increased the intracellular expression of IL-33. In conclusion, the release of IL-33 is tightly controlled and, in smokers, an altered activation of TLR4 may lead to an increased intracellular expression of IL-33 with a limited IL-33 release.
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy. Electronic address: pace@ibim.cnr.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Sano
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Sciarrino
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Scafidi
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chiappara
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.affiliation: School and Division of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gangemi
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: Dipartimento di Anestesia, Rianimazione e delle'Emergenze - Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Giarratano
authors.affiliation: Institute of Biomedicine and Molecular Immunology (IBIM) - National Research Council (CNR), Palermo, Italy.
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007124:Immunoenzyme Techniques; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Bronchial epithelial cell; COPD; Cigarette smoke; IL-33; Inflammation