Transcriptional inhibition of the beta-amyloid precursor protein by interferon-gamma.
Attenuating beta-amyloid precursor protein (beta-APP) gene expression may have relevance in diseases such as Alzheimer's disease, where beta-APP has been implicated in neuropathological processes. We report here on the transcriptional down-regulation of beta-APP by interferon-gamma (IFN-gamma) in SKNMC human neuroblastoma cells. Treatment of the cells with IFN-gamma resulted in a 85% dose-dependent inhibition of beta-APP promoter activity after 24 h of exposure, with no changes observed at 5 h. For comparison, additional cytokines and signaling agents were also investigated for effects on beta-APP promoter activity. Elevated levels of activity were observed after treatment with phorbol 12-myristate 13-acetate and basic fibroblast growth factor whereas no significant effects were seen after treatment with lipopolysaccharide or interleukin-1 beta. Thus, IFN-gamma was shown here to be a suppressor of beta-APP promoter activity and is the first cytokine reported to possess such down-regulating effects.
Ringheim
G E
GE
Neuroscience Therapeutic Area, Hoechst Marion Roussel, Inc., Somerville, New Jersey 08876, USA. ringhei1@brwhcc3.hcc.com
Szcepanik
A M
AM
Burgher
K L
KL
Petko
W
W
Heroux
J A
JA
Cavalieri
F
F
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015698:Genomic Library; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D013489:Suppression, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D007371:Interferon-gamma; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate