Portal de investigación
Xenobiotic metabolism in differentiated human bronchial epithelial cells
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Boei JJWA
- Vermeulen, S
- Klein, B
- Hiemstra, PS
- Verhoosel, RM
- Jennen DGJ
- Gmuender, H
- Vrieling, H
Grupos
Abstract
Differentiated human bronchial epithelial cells in air liquid interface cultures (ALI-PBEC) represent a promising alternative for inhalation studies with rodents as these 3D airway epithelial tissue cultures recapitulate the human airway in multiple aspects, including morphology, cell type composition, gene expression and xenobiotic metabolism. We performed a detailed longitudinal gene expression analysis during the differentiation of submerged primary human bronchial epithelial cells into ALI-PBEC to assess the reproducibility and inter-individual variability of changes in transcriptional activity during this process. We generated ALI-PBEC cultures from four donors and focussed our analysis on the expression levels of 362 genes involved in biotransformation, which are of primary importance for toxicological studies. Expression of various of these genes (e. g., GSTA1, ADH1C, ALDH1A1, CYP2B6, CYP2F1, CYP4B1, CYP4X1 and CYP4Z1) was elevated following the mucociliary differentiation of airway epithelial cells into a pseudo-stratified epithelial layer. Although a substantial number of genes were differentially expressed between donors, the differences in fold changes were generally small. Metabolic activity measurements applying a variety of different cytochrome p450 substrates indicated that epithelial cultures at the early stages of differentiation are incapable of biotransformation. In contrast, mature ALI-PBEC cultures were proficient in the metabolic conversion of a variety of substrates albeit with considerable variation between donors. In summary, our data indicate a distinct increase in biotransformation capacity during differentiation of PBECs at the air-liquid interface and that the generation of biotransformation competent ALI-PBEC cultures is a reproducible process with little variability between cultures derived from four different donors.
Datos de la publicación
- ISSN/ISSNe:
- 0340-5761, 1432-0738
- Tipo:
- Article
- Páginas:
- 2093-2105
- PubMed:
- 27738743
- Factor de Impacto:
- 1,541 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ARCHIVES OF TOXICOLOGY SPRINGER HEIDELBERG
Citas Recibidas en Web of Science: 25
Documentos
- No hay documentos
Filiaciones
Keywords
- Lung; Metabolic activity; Gene expression profiling; Bronchial epithelial cells; Cytochrome P450
Proyectos y Estudios Clínicos
BÚSQUEDA DE PATRONES METABONÓMICOS PARA LA RÁPIDA EVALUACIÓN DE LA CALIDAD DEL HÍGADO DONANTE, PREVIO AL IMPLANTE, Y LA SUBSECUENTE MONITORIZACIÓN DE SU EVOLUCIÓN POST TRASPLANTE
Investigador Principal: AGUSTÍN LAHOZ RODRÍGUEZ
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Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
602156_HECATOS_PE_FP7-HEALTH-2013-INNOVATI . 2013
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2014_0081_PE_ROTF_LAHOZ . 2014
DESARROLLO DE UNA ESTRATEGIA BASADA EN ANÁLISIS METABOLÓMICO PARA EVALUAR LA CALIDAD DEL HÍGADO DONANTE ANTES DE SU IMPLANTE. VALIDACIÓN CLÍNICA MEDIANTE ESTUDIO MULTICÉNTRICO PROSPECTIVO.
PI14/00026 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2015
ADQUISICIÓN DE UNA PLATAFORMA BIG DATA PARA EL ANÁLISIS Y LA GESTIÓN DE DATOS MULTI-ÓMICOS Y CLÍNICOS ORIENTADA A LA MEDICINA DE PRECISIÓN.
Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL
FUFE15-EE-3906 . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD . 2016
Cita
Boei J,Vermeulen S,Klein B,Hiemstra PS,Verhoosel RM,Jennen DGJ,LAHOZ A,Gmuender H,Vrieling H. Xenobiotic metabolism in differentiated human bronchial epithelial cells. Arch Toxicol. 2017. 91. (5):p. 2093-2105. IF:5,728. (1).