Induction of CD40 on human endothelial cells by Alzheimer's beta-amyloid peptides.
Growing evidence suggests that beta-amyloid (Abeta) peptides play a central role in mediating vascular endothelium dysfunction, but the extent to which immune mechanisms are involved in this process remains unclear. To explore such mechanisms, we incubated cultured human aortic endothelial cells (HAEC) with freshly solublized Abeta and examined expression of a central immunoregulatory molecule, CD40, in these cells using reverse transcriptase-polymerase chain reaction, Western immunoblotting, and Flow cytometry. Our results show that treatment of endothelial cells with Abeta1-40, Abeta1-42 or gamma interferon (IFN-gamma) results in a dose-dependent induction of endothelial CD40 expression. Furthermore, ligation of endothelial CD40 and simultaneous treatment of human endothelial cells with IFN-gamma or Abeta peptides leads to a significant release of interleukin-1beta (IL-1beta), a marker for endothelial cell activation. Since IL-1beta is an important inflammatory response mediator, these findings suggest that the functional role of Abeta-induced endothelial CD40 may be promotion of the inflammatory cascade in vascular endothelial cells.
Tan
J
J
The Roskamp Institute, University of South Florida, Tampa 33612, USA.
Town
T
T
Suo
Z
Z
Wu
Y
Y
Song
S
S
Kundtz
A
A
Kroeger
J
J
Humphrey
J
J
Crawford
F
F
Mullan
M
M
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity*; D015153:Blotting, Western; D019013:CD40 Antigens / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity*; D016133:Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D019013:CD40 Antigens; D007375:Interleukin-1; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D007371:Interferon-gamma