Deoxypodophyllotoxin inhibits the expression of intercellular adhesion molecule-1 induced by tumor necrosis factor-alpha in murine lung epithelial cells.
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.
Jin
Meihua
M
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Lee
Eunkyung
E
Yang
Ju Hye
JH
Lu
Yue
Y
Kang
SangGu
S
Chang
Young-Chae
YC
Lee
Seung Ho
SH
Suh
Seok-Jong
SJ
Kim
Cheorl-Ho
CH
Chang
Hyeun Wook
HW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D017930:Genes, Reporter; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C014451:deoxypodophyllotoxin; D011034:Podophyllotoxin