Deoxypodophyllotoxin inhibits the expression of intercellular adhesion molecule-1 induced by tumor necrosis factor-α in murine lung epithelial cells

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is associated with processes of inflammation. We investigated the effects of deoxypodophyllotoxin (DPT) on tumor necrosis factor-α (TNF-α) induced ICAM-1 expression in the mouse lung epithelial cell line, LA4. DPT (5 to 20 nM) inhibited TNF-α-induced ICAM-1 expression through nuclear factor-kappa B (NF-κB) in a dose-dependent manner and repressed ICAM-1 promoter activity. NF-κB reporter gene activity and DNA binding activity were also strongly inhibited. In addition, DPT inhibited degradation by the TNF-α induced inhibitory kB-α (IκB-α) in a concentration-dependent manner. Taken together with our previous results suggest DPT might provide a basis for novel anti-inflammatory drug development. © 2010 Pharmaceutical Society of Japan.