title: The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.
abstract: Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation.
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Radina
authors.initials: R
authors.lastname: Kostadinova
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Mathis
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Sewer
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Shoaib
authors.initials: S
authors.lastname: Majeed
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Diana
authors.initials: D
authors.lastname: Kuehn
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frentzel
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Merg
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Geertz
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Martin
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Ivanov
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland julia.hoeng@pmi.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
mesh_terms: D000368:Aged; D000826:Animal Testing Alternatives; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D046509:Tissue Culture Techniques; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D012906:Smoke
keywords: bronchial; nasal; organotypic; translational systems toxicology; whole cigarette smoke exposure