title: Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface.
abstract: The differentiated human airway epithelium consists of different cell types forming a polarized and pseudostratified epithelium. This is dramatically altered in chronic obstructive pulmonary disease (COPD), characterized by basal and goblet cell hyperplasia, and squamous cell metaplasia. The effect of cigarette smoke on human bronchial epithelial cell (HBEC) differentiation remains to be elucidated. We analysed whether cigarette smoke extract (CSE) affected primary (p)HBEC differentiation and function. pHBEC were differentiated at the air-liquid interface (ALI) and differentiation was quantified after 7, 14, 21, or 28 days by assessing acetylated tubulin, CC10, or MUC5AC for ciliated, Clara, or goblet cells, respectively. Exposure of differentiating pHBEC to CSE impaired epithelial barrier formation, as assessed by resistance measurements (TEER). Importantly, CSE exposure significantly reduced the number of ciliated cells, while it increased the number of Clara and goblet cells. CSE-dependent cell number changes were reflected by a reduction of acetylated tubulin levels, an increased expression of the basal cell marker KRT14, and increased secretion of CC10, but not by changes in transcript levels of CC10, MUC5AC, or FOXJ1. Our data demonstrate that cigarette smoke specifically alters the cellular composition of the airway epithelium by affecting basal cell differentiation in a post-transcriptional manner.
authors: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, University Hospital, Ludwig-Maximilians-University and Helmholtz Zentrum München, Member of the German Center for Lung Research, Max-Lebsche-Platz 31, 81377 Munich, Germany.
authors: Andrea C
authors: AC
authors: Schamberger
authors: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, University Hospital, Ludwig-Maximilians-University and Helmholtz Zentrum München, Member of the German Center for Lung Research, Max-Lebsche-Platz 31, 81377 Munich, Germany.
authors: Claudia A
authors: CA
authors: Staab-Weijnitz
authors: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, University Hospital, Ludwig-Maximilians-University and Helmholtz Zentrum München, Member of the German Center for Lung Research, Max-Lebsche-Platz 31, 81377 Munich, Germany.
authors: Nikica
authors: N
authors: Mise-Racek
authors: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, University Hospital, Ludwig-Maximilians-University and Helmholtz Zentrum München, Member of the German Center for Lung Research, Max-Lebsche-Platz 31, 81377 Munich, Germany.
authors: Oliver
authors: O
authors: Eickelberg
mesh_terms: D000107:Acetylation; D001980:Bronchi / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D012906:Smoke; D062789:Tobacco Products / Q000633:toxicity*; D014404:Tubulin / Q000378:metabolism; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism
chemical_list: C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; C507540:KRT14 protein, human; D053547:Keratin-14; C524678:MUC5AC protein, human; D055271:Mucin 5AC; C556389:SCGB1A1 protein, human; D012906:Smoke; D014404:Tubulin; D014598:Uteroglobin
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