In vitrosystems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures

Autor:	Alain Sewer, Diana Kuehn, Marja Talikka, Carole Mathis, Julia Hoeng, Radina Kostadinova, Shoaib Majeed, Stefan Frentzel, Marcel Geertz, Nikolai V. Ivanov, Walter K. Schlage, Yang Xiang, Anita R. Iskandar, Manuel C. Peitsch
Rok vydání:	2014
Předmět:	Pathology medicine.medical_specialty Health Toxicology and Mutagenesis organotypic cultures Air–liquid interface Inflammation In Vitro Techniques Biology Toxicology Epithelium transcriptomics oral keratinocytes In vivo Smoke Tobacco medicine Humans Oral mucosa Periodontitis Lung Mouth Mucosa Buccal administration causal biological network model medicine.disease In vitro medicine.anatomical_structure medicine.symptom Transcriptome Research Article
Zdroj:	Toxicology Mechanisms and Methods
ISSN:	1537-6524 1537-6516
DOI:	10.3109/15376516.2014.943441
Popis:	Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air–liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::150f48cf63c0e6244bcb488e73c0bcfc https://doi.org/10.3109/15376516.2014.943441 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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