PMID- 8694821 OWN - NLM STAT- MEDLINE DCOM- 19960829 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 224 IP - 1 DP - 1996 Jul 5 TI - Transcriptional inhibition of the beta-amyloid precursor protein by interferon-gamma. PG - 246-51 AB - 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. FAU - Ringheim, G E AU - Ringheim GE AD - Neuroscience Therapeutic Area, Hoechst Marion Roussel, Inc., Somerville, New Jersey 08876, USA. ringhei1@brwhcc3.hcc.com FAU - Szcepanik, A M AU - Szcepanik AM FAU - Burgher, K L AU - Burgher KL FAU - Petko, W AU - Petko W FAU - Heroux, J A AU - Heroux JA FAU - Cavalieri, F AU - Cavalieri F LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Interleukin-1) RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.13.12.- (Luciferases) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Amyloid beta-Protein Precursor/*biosynthesis/*genetics MH - Cell Line MH - Cell Survival MH - Female MH - Fibroblast Growth Factor 2/pharmacology MH - Genomic Library MH - Humans MH - Interferon-gamma/*pharmacology MH - Interleukin-1/pharmacology MH - Kinetics MH - Lipopolysaccharides/pharmacology MH - Luciferases/biosynthesis MH - Placenta/metabolism MH - Pregnancy MH - Promoter Regions, Genetic MH - Recombinant Proteins/biosynthesis MH - Suppression, Genetic MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transcription, Genetic/*drug effects MH - Transfection EDAT- 1996/07/05 00:00 MHDA- 1996/07/05 00:01 CRDT- 1996/07/05 00:00 PHST- 1996/07/05 00:00 [pubmed] PHST- 1996/07/05 00:01 [medline] PHST- 1996/07/05 00:00 [entrez] AID - S0006-291X(96)91015-3 [pii] AID - 10.1006/bbrc.1996.1015 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1996 Jul 5;224(1):246-51. doi: 10.1006/bbrc.1996.1015.