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

H A Smits; N M de Vos; J W Wat; T van der Bruggen; J Verhoef; H S Nottet

doi:10.1016/s0165-5728(01)00254-5

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

J Neuroimmunol. 2001 Apr 2;115(1-2):144-51. doi: 10.1016/s0165-5728(01)00254-5.

Authors

H A Smits¹, N M de Vos, J W Wat, T van der Bruggen, J Verhoef, H S Nottet

Affiliation

¹ Section Neuroimmunology, Room G04.614, Eijkman-Winkler Institute, University Medical Center Utrecht, Heidelberglaan 100, NL-3584 CX, Utrecht, The Netherlands. [email protected]

PMID: 11282164
DOI: 10.1016/s0165-5728(01)00254-5

Abstract

In this study, the intracellular signal transduction pathways leading to the 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 MAPK signal transduction pathways as well as PKC are involved in the amyloid-beta-stimulated superoxide anion production. In contrast, only ERK 1/2 MAPK seems to be involved in TNF-alpha 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / pharmacology*
Cells, Cultured
Enzyme Inhibitors / pharmacology
Humans
Macrophages / cytology
Macrophages / drug effects*
Macrophages / metabolism*
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Peptide Fragments / pharmacology*
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / metabolism
Second Messenger Systems / drug effects
Second Messenger Systems / physiology*
Signal Transduction / drug effects
Signal Transduction / physiology
Superoxides / metabolism*
Tumor Necrosis Factor-alpha / metabolism*
p38 Mitogen-Activated Protein Kinases

Substances

Amyloid beta-Peptides
Enzyme Inhibitors
Peptide Fragments
Tumor Necrosis Factor-alpha
amyloid beta-protein (1-42)
Superoxides
Protein Kinase C
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases