Hydroxypropyl Cyclodextrin Improves Amiodarone-induced Aberrant Lipid Homeostasis of Alveolar Cells

Alveolar epithelial type II (AT2) cells secrete pulmonary surfactant via lamellar bodies (LBs). Abnormalities in LBs are associated with pulmonary disorders, including fibrosis. However, high-content screening (HCS) for LB abnormalities is limited by the lack of understanding of AT2 cell functions. In the present study, we have developed LB cells harboring LB-like organelles that secrete surfactant proteins. These cells were more similar to AT2 cells than to parental A549 cells. LB cells recapitulated amiodarone (AMD)induced LB enlargement, similar to AT2 cells of patients exposed to AMD. To reverse AMD-induced LB abnormalities, we performed HCS of approved drugs and identified 2-hydroxypropyl-beta-cyclodextrin (HP beta CD), a cyclic oligosaccharide, as a potential therapeutic agent. A transcriptome analysis revealed that HP beta CD modulates lipid homeostasis. In addition, HP beta CD inhibited AMD-induced LB abnormalities in human induced pluripotent stem cell-derived AT2 cells. Our results demonstrate that LB cells are useful for HCS and suggest that HP beta CD is a candidate therapeutic agent for AMD-induced interstitial pneumonia.

Automated summary

The study developed LB-like cells for investigating LB abnormalities and potential treatments. HPβCD was identified as a potential therapeutic agent for AMD-induced interstitial pneumonia.