GSE175878
Toxicological Transcriptome of Human Airway Constructs After Exposure to Indoor Air Particulate Matter: In Search of Relevant Pathways of Moisture Damage -Associated Health Effects
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 - Alongside general toxicological markers, 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.  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 airway constructs to three doses (1:16, 1:8, 1:4) of PM from moisture-damaged (index) and non-moisture-damaged (reference) houses. The RNA of exposed constructs was sequenced targeting toxicology -related genes. We did groupwise comparisons between index and reference houses and pairwise comparisons in matched index/reference houses. We analyzed general toxicological markers and imaged the constructs with electron microscopy.  Results - In pairwise comparison, several genes were differentially expressed. Genes related to multiple toxicological pathways were highlighted, while none of the genes was consistently expressed in all the comparisons. In groupwise comparison, CYP1A1 was statistically significantly over-expressed in index houses at all doses (dose 1:16 log2FC = 0.007, padj = 0.03; dose 1:8 log2FC = 0.077, padj = 0.018; dose 1:4 log2FC = 0.270, padj = 0.002) and NFKB1 at the highest dose 1:4 (log2FC = 0.124, padj = 0.029). General toxicological markers did not separate the index/reference houses.  Discussion - The exposure to PM from index houses activates toxicology -related genes in airway constructs. While 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. Overall design: Human airway constructs (differentiated from normal human bronchial epithelial [NHBE] cells) were exposed to three doses (1:16, 1:8, 1:4) of indoor air particulate matter from moisture-damaged (index) and non-moisture-damaged (reference) houses in synthetic lung lining fluid, and RNA-sequenced in 3-4 replicates, targeting toxicology -related genes.