Didecyldimethylammonium chloride (
DDAC) is a representative dialkyl-
quaternary ammonium compound that is used as a
disinfectant against several pathogens and is also used in commercial, industrial, and residential settings. We previously investigated toxicity on air way system following single instillation of
DDAC to the lungs in mice, and found that
DDAC causes
pulmonary injury, which is associated with altered
antioxidant antimicrobial responses; the inflammatory phase is accompanied or followed by fibrotic response. The present study was conducted to monitor
transforming growth factor-β (TGF-β) signaling in
pulmonary fibrosis induced by
DDAC. Mice were intratracheally instilled with
DDAC and sacrificed 1, 3, or 7 days
after treatment to measure TGF-β signaling. In order to further evaluate TGF-β signaling, we treated isolated mouse lung fibroblasts with
DDAC. Fibrotic foci were observed in the lungs on day 3, and were widely extended on day 7, with evidence of increased α-smooth muscle actin-positive mesenchymal cells and upregulation of
Type I procollagen mRNA. Developing fibrotic foci were likely associated with increased expression of Tgf-β1
mRNA, in addition to decreased expression of Bone morphogenetic protein-7
mRNA. In fibrotic lung samples, the expression of phosphorylated SMAD2/3 was considerably higher than that of phosphorylated SMAD1/5. In isolated lung fibroblasts, the
mRNA levels of Tgf-β1 were specifically increased by
DDAC treatment, which prolonged phosphorylation of SMAD2/3. These effects were abolished by treatment with SD208 - a TGF-βRI
kinase inhibitor. The results suggest that
DDAC induces
pulmonary fibrosis in association with TGF-β signaling.