PrP106-126 and Aβ 1-42 peptides induce BV-2 microglia chemotaxis and proliferation.
Transmissible spongiform encephalopathies (TSEs) and Alzheimer's disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrP(Sc) and Aβ in TSEs and AD, respectively). To better understand how protein aggregates can modulate microglial processes in these diseases, we treated BV-2 microglia with PrP(106-126) or Aβ1-42 peptides individually at three different concentrations (25-100 μM PrP(106-12) and 2.5-10 μM Aβ1-42) or with a mixture of PrP(106-126) and Aβ1-42 peptides at specified concentrations for 6-24 h. BV-2 microglia chemotaxis, proliferation, and monocyte chemoattractant protein-1 and transforming growth factor-β1 (TGF-β1) secretion were measured and compared between treatments. The results demonstrate that PrP(106-126) and Aβ1-42 peptides induce increases in all four parameters from 6 to 12 h. However, the measured indices plateaued beyond 12 h in BV-2 cells treated >50 μM PrP or >5 μM Aβ1-42, with the exception of TGF-β1 secretion, which continued to increase gradually. Overall, the results of this study indicate that these two peptides may mutually inhibit microglial chemotaxis and proliferation simultaneously via changes induced at the protein level.
National Animal TSE Lab, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Jian
J
Tu
LiFeng
L
Yang
XiangMei
X
Zhou
KeZong
K
Qi
JinGuo
J
Wang
Mohammed
M
Kouadir
LiHua
L
Xu
XiaoMin
X
Yin
DeMing
D
Zhao
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018932:Chemokine CCL2; D010446:Peptide Fragments; D011328:Prions; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42); C082632:prion protein (106-126)