Intracellular pathways involved in TNF-alpha and superoxide anion release by A beta(1-42)-stimulated primary human macrophages

In this study, the intracellular signal transduction pathways leading to th e production of TNF-alpha and superoxide anions by amyloid-beta -stimulated primary human monocyte-derived macrophages was investigated. Using Western blotting and specific inhibitors it is shown that both ERK 1/2 and p38 MAP K signal transduction pathways as well as PKC are involved in the amyloid-b eta -stimulated superoxide anion production. In contrast. only ERK 1/2 MAPK seems to be involved in TNF-alpha production: questioning the connection b etween PKC and ERK 1/2 activation. Our results suggest the use of ERK 1/2 M APK inhibitors in the prevention of macrophage activation in the context of Alzheimer's disease. (C) 2001 Elsevier Science B.V. All rights reserved.