title: Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease.
abstract: Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of smokers develop the disease. We tested the hypothesis that the response of the bronchial epithelium to cigarette smoke (CS) differs in patients with COPD. Such a difference might explain in part why only some cigarette smokers develop the disease. We established primary explant cultures of human bronchial epithelial cells (HBEC) from biopsy material obtained from never-smokers who had normal pulmonary function, smokers with normal pulmonary function, and smokers with COPD, and exposed these for 20 min to CS or air. Measurements were subsequently made over a period of 24 h of transepithelial permeability and release of interleukin (IL)-1beta and soluble intercellular adhesion molecule-1 (sICAM-1). In addition, intracellular reduced glutathione (GSH) levels were measured after 24 h incubation. Exposure to CS increased the permeability of these cultures in all study groups, but the most marked effect was observed in cultures from patients with COPD (mean increase, 85.5%). The smallest CS-induced increase in the permeability was observed in HBEC cultured from smokers with normal pulmonary function (mean, 25.0%), and this was significantly lower than that of HBEC from never-smokers (mean, 53.4%) (P<0.001). Compared with exposure to air, exposure to CS led to a significantly increased release of these mediators from cultures of the never-smoker group (mean 250.0% increase in IL-1beta and mean 175.3% increase in sICAM-1 24 h after exposure) and COPD group (mean 383.3% increase in IL-1beta and mean 97.4% increase in sICAM-1 24 h after exposure). In contrast, CS exposure did not influence significantly the release of either mediator from the cells of smokers with normal pulmonary function. Levels of intracellular GSH were significantly higher in cultures of HBEC derived from smokers, both those with normal pulmonary function and those with COPD, compared with cultures from healthy never-smokers. Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures. However, the fall in intracellular GSH was significantly greater in cells from patients with COPD (mean 72.9% decrease) than in cells from never-smokers (mean 61.4% decrease; P = 0.048) or smokers with normal pulmonary function (mean 43.9% decrease; P = 0.02). These results suggest that whereas smokers with or without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effects of CS in reducing GSH levels and causing increased permeability and release of proinflammatory mediators such as IL-1beta and sICAM-1.
authors.affiliation: Academic Department of Respiratory Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, London, United Kingdom. Csaba.Rusznak@mcmail.vanderbilt.edu
authors.forename: C
authors.initials: C
authors.lastname: Rusznak
authors.forename: P R
authors.initials: PR
authors.lastname: Mills
authors.forename: J L
authors.initials: JL
authors.lastname: Devalia
authors.forename: R J
authors.initials: RJ
authors.lastname: Sapsford
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
authors.forename: S
authors.initials: S
authors.lastname: Lozewicz
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010947:Plants, Toxic; D012906:Smoke; D012907:Smoking / Q000378:metabolism; D014026:Nicotiana
chemical_list: D007375:Interleukin-1; D012906:Smoke; D018799:Intercellular Adhesion Molecule-1; D005978:Glutathione