Intracellular pathways involved in TNF-alpha and superoxide anion release by Abeta(1-42)-stimulated primary human macrophages.
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.
Smits
H A
HA
Section Neuroimmunology, Room G04.614, Eijkman-Winkler Institute, University Medical Center Utrecht, Heidelberglaan 100, NL-3584 CX, Utrecht, The Netherlands. h.a.smits@lab.azu.nl
de Vos
N M
NM
Wat
J W
JW
van der Bruggen
T
T
Verhoef
J
J
Nottet
H S
HS
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D013481:Superoxides; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases