Transcriptional inhibition of the beta-amyloid precursor protein by interferon-gamma.

Abstract Attenuating beta-amyloid precursor protein (β-APP) gene expression may have relevance in diseases such as Alzheimer's disease, where β-APP has been implicated in neuropathological processes. We report here on the transcriptional down-regulation of β-APP by interferon-gamma (IFN-γ) in SKNMC human neuroblastoma cells. Treatment of the cells with IFN-γ resulted in a 85% dose-dependent inhibition of β-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 β-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-γ was shown here to be a suppressor of β-APP promoter activity and is the first cytokine reported to possess such down-regulating effects.