Title: | Toxicological transcriptome of human airway constructs after exposure to indoor air particulate matter: In search of relevant pathways of moisture damage-associated health effects |
Author(s): | Nordberg ME; Taubel M; Heikkinen S; Jalkanen K; Kolio A; Stranger M; Leppanen H; Hyvarinen A; Huttunen K; |
Address: | "Department of Environmental and Biological Sciences, University of Eastern Finland (UEF), Yliopistonranta 1, FI-70211 Kuopio, Finland. Electronic address: maria-elisa.nordberg@uef.fi. Environmental Health Unit, Finnish Institute for Health and Welfare, Neulaniementie 4, FI-70701 Kuopio, Finland. School of Medicine, Institutes of Clinical Medicine and Biomedicine, University of Eastern Finland (UEF), Yliopistonranta 1, FI-70211 Kuopio, Finland. Renovatek Oy, Korkeakoulunkatu 1, FI-33720 Tampere, Finland. Environmental Risk and Health Unit, VITO, Boeretang 200, 2400 Mol, Belgium. Department of Environmental and Biological Sciences, University of Eastern Finland (UEF), Yliopistonranta 1, FI-70211 Kuopio, Finland" |
DOI: | 10.1016/j.envint.2021.106997 |
ISSN/ISBN: | 1873-6750 (Electronic) 0160-4120 (Linking) |
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: | "*Air Pollutants/analysis/toxicity *Air Pollution, Indoor/analysis Humans Particulate Matter/analysis/toxicity Transcriptome Gene expression Health effects In vitro Indoor air Moisture damage Particulate matter;" |
Notes: | "MedlineNordberg, Maria-Elisa Taubel, Martin Heikkinen, Sami Jalkanen, Kaisa Kolio, Arto Stranger, Marianne Leppanen, Hanna Hyvarinen, Anne Huttunen, Kati eng Research Support, Non-U.S. Gov't Netherlands 2022/01/08 Environ Int. 2022 Jan; 158:106997. doi: 10.1016/j.envint.2021.106997. Epub 2021 Nov 26" |