title: IL-8 production in response to cigarette smoke is decreased in epithelial cells from COPD patients.
abstract: Cigarette smoke is the principal cause of chronic obstructive pulmonary disease (COPD), a disorder characterized by airway inflammation. As epithelial cells are the first line of defense against foreign material, the response of normal epithelial cells to smoke has been extensively studied. However, little is known about how epithelial cells derived from COPD patients respond to ongoing smoke exposure. This study was aimed at comparing the intracellular response of normal human bronchial/tracheal epithelial cells (NHBE) and COPD-diseased human bronchial/tracheal epithelial cells (DHBE) to cigarette smoke. NHBE and DHBE cells were treated with cigarette smoke condensate (CSC) for 24 h. IL-8 production was measured by ELISA and western blot was used to measure TLR4 expression. Cells were pretreated with CLI-095, a TLR4 inhibitor, or the signaling pathway inhibitors PD184352, Helenalin, or PI-103, which inhibit the ERK1/2, NF-κB and PI3K pathways, respectively. NHBE cells increased IL-8 production in a dose-dependent manner in response to CSC while DHBE cells did not show any significant difference and had a much lower production of IL-8 in response to CSC compared to NHBE cells. There was no change in TLR4 expression with CSC exposure. CLI-095 and PD184352 attenuated IL-8 secretion, indicating that CSC-induced inflammation is both TLR4- and ERK1/2-dependent. These results demonstrate that NHBE and DHBE cells differentially respond to cigarette smoke. DHBE cells exhibit a dampened IL-8 release, indicating that COPD is associated with a reduced capacity of airway epithelial cells to respond to foreign material.
authors.affiliation: Meakins-Christie Laboratories, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nadigel
authors.forename: Séverine
authors.initials: S
authors.lastname: Audusseau
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
authors.forename: David H
authors.initials: DH
authors.lastname: Eidelman
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014132:Trachea / Q000166:cytology / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: COPD; Cigarette smoke; Epithelial cells; Interleukin-8; Toll-like receptors