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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / isolation & purification
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Anti-Inflammatory Agents / pharmacology*
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Apiaceae / chemistry
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Cell Line
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DNA-Binding Proteins / antagonists & inhibitors
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Genes, Reporter
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I-kappa B Proteins / antagonists & inhibitors
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism*
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Lung / cytology
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Mice
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Plant Roots
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Podophyllotoxin / analogs & derivatives*
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Podophyllotoxin / isolation & purification
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Podophyllotoxin / pharmacology
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Promoter Regions, Genetic
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RNA, Messenger / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Substances
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Anti-Inflammatory Agents
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DNA-Binding Proteins
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Drugs, Chinese Herbal
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I-kappa B Proteins
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NF-kappa B
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Nfkbia protein, mouse
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Plant Extracts
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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NF-KappaB Inhibitor alpha
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deoxypodophyllotoxin
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Podophyllotoxin