Evidence map›Paper›PMID 27738743›Full record

ArticleArchives of toxicology2017

Xenobiotic metabolism in differentiated human bronchial epithelial cells.

Jan J W A Boei, Sylvia Vermeulen, Binie Klein, Pieter S Hiemstra, Renate M Verhoosel, Danyel G J Jennen, Agustin Lahoz, Hans Gmuender, Harry Vrieling

Abstract read
In one paragraph

Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. Article
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  8. An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jan J W A BoeiDepartment of Human Genetics, Leiden University Medical Center, Postal Zone S4-P, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Sylvia VermeulenDepartment of Human Genetics, Leiden University Medical Center, Postal Zone S4-P, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Binie KleinDepartment of Human Genetics, Leiden University Medical Center, Postal Zone S4-P, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Pieter S HiemstraDepartment of Pulmonology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Renate M VerhooselDepartment of Pulmonology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Danyel G J JennenDepartment of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
Agustin LahozUnidad de Hepatología Experimental, Instituto de Investigación Sanitaria-Fundación Hospital La Fe, 46009, Valencia, Spain.
Hans GmuenderGenedata AG, 4053, Basel, Switzerland.
Harry VrielingDepartment of Human Genetics, Leiden University Medical Center, Postal Zone S4-P, PO Box 9600, 2300 RC, Leiden, The Netherlands. h.vrieling@lumc.nl.ORCID http://orcid.org/0000-0002-3034-2664

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Benz(a)AnthracenesBenzo(a)pyreneBiotransformationBronchiCell Culture TechniquesCell DifferentiationCytochromesEnzymesEpithelial CellsGene Expression RegulationHumansPolychlorinated DibenzodioxinsReproducibility of ResultsXenobiotics1,2,5,6-dibenzanthraceneBenz(a)AnthracenesBenzo(a)pyrenecytochrome P420CytochromesEnzymesPolychlorinated DibenzodioxinsXenobioticsBronchial epithelial cellsCytochrome P450Gene expression profilingLungMetabolic activity

Identifiers

PMID27738743
PMCPMC5399058

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.