Interleukin-1 beta dissociates beta-amyloid precursor protein and beta-amyloid peptide secretion.
A heightened production of interleukin 1 beta (IL-1 beta) has been reported in microglial-associated amyloid deposits in Alzheimer's disease (AD) brains. These plaques are composed predominantly of beta/A4 peptide derived from beta-amyloid precursor protein (beta APP). We demonstrate that short-term (1 h) IL-1 beta-treatment increases beta APPs secretion and concomitantly decreases cell-associated beta APP in human H4 neuroglioma cells. Long-term (5 h) IL-1 beta treatment did not alter secreted or cell-associated beta APP content. In contrast, the secretion of beta/A4-containing epitope was not affected by short-term IL-1 beta stimulation; however, long-term IL-1 beta treatment decreased the amount of beta/A4-containing epitope secreted from the cells. These results show that IL-1 beta modifies the processing and secretion of beta APP to exacerbate perhaps the neuropathology of AD.
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105.
J P
JP
Vasilakos
R T
RT
Carroll
M R
MR
Emmerling
P D
PD
Doyle
R E
RE
Davis
K S
KS
Kim
B D
BD
Shivers
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005910:Glioma; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D007375:Interleukin-1