Activation of toxicology-related genes in human airway constructs after exposure to indoor air particulate matter from moisture-damaged houses

Abstract

Exposure to altered microbial characteristics as a consequence of moisture damage indoors is considered to be a key factor behind the observed health effects. Nevertheless, the connection between moisture damage, microbial exposure, adverse health effects and pathophysiological mechanisms is still unknown. Our aim was to study toxicology-related gene expression in airway epithelium after exposure to indoor particulate matter (PM) sampled from moisture-damaged houses.

Normal human bronchial epithelial cells (NHBE) were differentiated in air-liquid interface for 22 days. The airway constructs were exposed (24 h) to three doses of indoor PM (1:16, 1:8, 1:4) sampled from nine moisture-damaged vs. non-moisture-damaged -house pairs, each pair having similar construction, age, and geographical location. The RNA of the airway constructs was extracted and sequenced for 386 genes associated with toxicological responses.

In the pairwise comparison, 43 genes were differentially expressed upon exposure to indoor PM from damaged versus control homes; eight genes were differentially expressed more than five-fold. Both up- and down-regulation was demonstrated among the expressed genes. Most of the expressed genes were related to immunotoxicity; also genes related to steatosis, cholestasis, phospholipidosis and necrosis were affected. None of the genes was expressed systematically in all of the house pair -comparisons. The results indicate that the exposure to indoor PM from moisture-damaged houses activates especially immune defense-related genes in human airway constructs, but the effect does not manifest in the same way in every moisture-damaged house.