Toxicological transcriptome of human airway constructs after exposure to indoor air particulate matter: In search of relevant pathways of moisture damage-associated health effects.
Gene expression
Health effects
In vitro
Indoor air
Moisture damage
Particulate matter
Journal
Environment international
ISSN: 1873-6750
Titre abrégé: Environ Int
Pays: Netherlands
ID NLM: 7807270
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
18
07
2021
revised:
16
11
2021
accepted:
20
11
2021
entrez:
7
1
2022
pubmed:
8
1
2022
medline:
11
1
2022
Statut:
ppublish
Résumé
Multiple health effects are associated with moisture damage in buildings. Studies explaining these associations and cell-level mechanisms behind the observed health effects are urgently called for. We focused on characterizing gene expression in human airway epithelium after exposure to indoor air particulate matter (PM) sampled from houses with and without moisture damage, alongside determination of general toxicological markers. We performed detailed technical building inspections in 25 residential houses and categorized them based on the detection of moisture damages and the probability of occupant exposure. PM sampling was complemented by microbiological and volatile organic compound assessment. We exposed human airway constructs to three dilutions (1:16, 1:8, 1:4) of collected PM from moisture-damaged (index) and non-moisture-damaged (reference) houses and imaged selected constructs with electron microscopy. We analyzed general toxicological markers and the RNA of exposed constructs was sequenced targeting genes associated with toxicological pathways. We did groupwise comparisons between index and reference houses and pairwise comparisons in matched index/reference houses. In groupwise comparison, gene Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) was statistically significantly over-expressed in index houses at all dilutions of collected PM and Nuclear Factor Kappa B Subunit 1 (NFKB1) at dilution 1:4 of collected PM. In pairwise index/reference house comparison, several genes related to multiple toxicological pathways were activated, largest expression differences seen for CYP1A1. However, none of the genes was consistently expressed in all the matched pairs, and general toxicological markers did not differentiate index and reference houses. The exposure to PM from index houses activated toxicology -related genes in airway constructs. Differential expression was not consistent among all the index/reference pairs, possibly due to compositional differences of bioactive particles. Our study highlights CYP1A1 and NFKB1 as potential targets in moisture damage -associated cellular responses.
Sections du résumé
BACKGROUND
Multiple health effects are associated with moisture damage in buildings. Studies explaining these associations and cell-level mechanisms behind the observed health effects are urgently called for.
OBJECTIVES
We focused on characterizing gene expression in human airway epithelium after exposure to indoor air particulate matter (PM) sampled from houses with and without moisture damage, alongside determination of general toxicological markers.
METHODS
We performed detailed technical building inspections in 25 residential houses and categorized them based on the detection of moisture damages and the probability of occupant exposure. PM sampling was complemented by microbiological and volatile organic compound assessment. We exposed human airway constructs to three dilutions (1:16, 1:8, 1:4) of collected PM from moisture-damaged (index) and non-moisture-damaged (reference) houses and imaged selected constructs with electron microscopy. We analyzed general toxicological markers and the RNA of exposed constructs was sequenced targeting genes associated with toxicological pathways. We did groupwise comparisons between index and reference houses and pairwise comparisons in matched index/reference houses.
RESULTS
In groupwise comparison, gene Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) was statistically significantly over-expressed in index houses at all dilutions of collected PM and Nuclear Factor Kappa B Subunit 1 (NFKB1) at dilution 1:4 of collected PM. In pairwise index/reference house comparison, several genes related to multiple toxicological pathways were activated, largest expression differences seen for CYP1A1. However, none of the genes was consistently expressed in all the matched pairs, and general toxicological markers did not differentiate index and reference houses.
DISCUSSION
The exposure to PM from index houses activated toxicology -related genes in airway constructs. Differential expression was not consistent among all the index/reference pairs, possibly due to compositional differences of bioactive particles. Our study highlights CYP1A1 and NFKB1 as potential targets in moisture damage -associated cellular responses.
Identifiants
pubmed: 34991257
pii: S0160-4120(21)00622-X
doi: 10.1016/j.envint.2021.106997
pii:
doi:
Substances chimiques
Air Pollutants
0
Particulate Matter
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106997Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.