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

Biol Pharm Bull. 2010;33(1):1-5. doi: 10.1248/bpb.33.1.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Apiaceae / chemistry
  • Cell Line
  • DNA-Binding Proteins / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Genes, Reporter
  • I-kappa B Proteins / antagonists & inhibitors
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lung / cytology
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / isolation & purification
  • Podophyllotoxin / pharmacology
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • DNA-Binding Proteins
  • Drugs, Chinese Herbal
  • I-kappa B Proteins
  • NF-kappa B
  • Nfkbia protein, mouse
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • deoxypodophyllotoxin
  • Podophyllotoxin