Intracellular pathways involved in TNF-α and superoxide anion release by Aβ(1–42)-stimulated primary human macrophages

• Published in: Journal of neuroimmunology Vol. 115; no. 1; pp. 144 - 151
• Main Authors: Smits, Hessel A., de Vos, N.Machiel, Wat, Jesse W.Y., van der Bruggen, Tjomme, Verhoef, Jan, Nottet, Hans S.L.M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 02.04.2001
• Subjects: Alzheimer's disease; extracellular signal-regulated kinase; Kinases; Signal transduction; TNF-α; β-Amyloid; PKG, protein kinase G; PKC, protein kinase C; NGF, nerve growth factor; SDS, sodium dodecyl sulfate; Kinases; TNF-α, tumor necrosis factor α; Aβ, amyloid-beta; IL-1β, interleukin-1β; Signal transduction; ERK, extracellular signal-regulated kinase; NF-κB, nuclear factor-κB; TNF-α; AD, Alzheimer's disease; NO, nitric oxide; PVDF, polyvinylidene difluoride; TGF-β, transforming growth factor-β; bFGF, basic fibroblast growth factor; MCP-1, monocyte chemoattractant protein-1; β-Amyloid; ROS, reactive oxygen species; Alzheimer's disease; MAPK, mitogen-activated protein kinase; PKA, protein kinase A
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(01)00254-5

In this study, the intracellular signal transduction pathways leading to the production of TNF-α and superoxide anions by amyloid-β-stimulated primary human monocyte-derived macrophages was investigated. Using Western blotting and specific inhibitors it is shown that both ERK 1/2 and p38 MAPK signal transduction pathways as well as PKC are involved in the amyloid-β-stimulated superoxide anion production. In contrast, only ERK 1/2 MAPK seems to be involved in TNF-α production: questioning the connection between PKC and ERK 1/2 activation. Our results suggest the use of ERK 1/2 MAPK inhibitors in the prevention of macrophage activation in the context of Alzheimer's disease.