title: Human Reconstituted Nasal Epithelium, a promising in vitro model to assess impacts of environmental complex mixtures.
abstract: Considering the impact of respiratory diseases around the world, appropriate experimental tools to help understand the mechanisms involved in such diseases are becoming essential. Our aim was to investigate the cellular and morphological reactivity of a human Reconstituted Nasal Epithelium (hRNE) to evaluate the impact of environmental complex mixture (ECM), with tobacco smoke as a model, after three weeks of repeated exposures. Staining of hRNE showed a multilayered ciliated epithelium, with a regular cilia beats, and a mucus production. When hRNE was exposed to ECM for 5 min once or twice a week, during 3 weeks, significant changes occurred: IL-8 production significantly increased 24h after the first exposure compared with Air-exposure and only during the first week, without any loss of tissue integrity. Immunostaining of F-actin cytoskeleton showed a modification in cellular morphology (number and diameter). Taken together our results indicate that hRNE is well suited to study the cellular and morphological effects of repeated exposures to an environmental complex mixture. Human reconstituted epithelium models are currently the best in vitro representation of human respiratory tract physiology, and also the most robust for performing repeated exposures to atmospheric pollutants.
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie de Paris, EA 4064, Laboratoire de Santé Publique et Environnement, Paris, France; Agence de l'environnement et de la Maîtrise de l'Energie (ADEME), Angers, France. Electronic address: gaelle.bardet@laposte.net.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bardet
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie de Paris, Cellular and Molecular Imaging Platform, UMS 3612 CNRS, US25 INSERM, Paris, France. Electronic address: virginie.mignon@parisdescartes.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mignon
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie de Paris, EA 4064, Laboratoire de Santé Publique et Environnement, Paris, France. Electronic address: isabelle.momas@parisdescartes.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Momas
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie de Paris, EA 4064, Laboratoire de Santé Publique et Environnement, Paris, France. Electronic address: sophie.achard@parisdescartes.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Achard
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie de Paris, EA 4064, Laboratoire de Santé Publique et Environnement, Paris, France; AP-HP, Hôpital Bichat, Biochimie, Paris, France. Electronic address: nathalie.seta@parisdescartes.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Seta
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
chemical_list: D000393:Air Pollutants; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014028:Tobacco Smoke Pollution; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase
keywords: 3D-in vitro model; Air–liquid exposure; Environmental complex mixture; Human Reconstituted Nasal Epithelium; Repeated exposures