Toxicological transcriptome of human airway constructs after exposure to indoor air particulate matter: In search of relevant pathways of moisture damage-associated health effects

Abstract

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.

Keywords: Gene expression; Health effects; In vitro; Indoor air; Moisture damage; Particulate matter.