Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.
Maria-Elisa NordbergMartin TäubelPasi I JalavaKelly BéruBéArja TervahautaAnne HyvärinenKati HuttunenPublished in: Indoor air (2020)
In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi-permeable cell culture membranes, to four doses of indoor air PM in the air-liquid interface. We analyzed the chemokine interleukin-8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non-complaint residential environment over 1 week. Sample collection was concomitant with monitoring size-segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up-regulation of 34 genes and down-regulation of 17 genes when compared to blank sampler control exposure. The five most up-regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure.
Keyphrases
- particulate matter
- air pollution
- endothelial cells
- genome wide
- induced pluripotent stem cells
- pluripotent stem cells
- electron microscopy
- single cell
- cystic fibrosis
- oxidative stress
- rna seq
- induced apoptosis
- microbial community
- transcription factor
- drug delivery
- cell death
- clinical trial
- pulmonary hypertension
- peripheral blood
- cell proliferation
- randomized controlled trial
- endoplasmic reticulum stress
- mass spectrometry
- signaling pathway
- molecularly imprinted
- ionic liquid
- nucleic acid
- high resolution
- pi k akt