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 her e on the transcriptional down-regulation of beta-APP by interferon-gam ma (IFN-gamma) in SKNMC human neuroblastoma cells. Treatment of the ce lls with IFN-gamma resulted in a 85% dose-dependent inhibition of beta -APP promoter activity after 24 h of exposure, with no changes observe d at 5 h. For comparison, additional cytokines and signaling agents we re also investigated for effects on beta-APP promoter activity. Elevat ed levels of activity were observed after treatment with phorbol 12-my ristate 13-acetate and basic fibroblast growth factor whereas no signi ficant effects were seen after treatment with lipopolysaccharide or in terleukin-1 beta. Thus, IFN-gamma was shown here to be a suppressor of beta-APP promoter activity and is the first cytokine reported to poss ess such down-regulating effects. (C) 1996 Academic Press, Inc.