The influence of tumour necrosis factor- α (TNF-α) on amyloid-β (Aβ)-degrading enzymes in vitro.
Pro-inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), are increased in serum and CSF in Alzheimer's disease (AD). We investigated the effect of TNF-α on gene and protein expression levels of Aβ degrading enzymes (ACE, ECE-1, ECE- 2, IDE and NEP) in vitro. Differentiated (DC) and non-differentiated (NDC) neuroblastoma cells (SH-SY5Y) were exposed to TNF-α for 15 minutes and 3 hours and protein and gene expression levels measured using western blotting or sandwich ELISA (ECE-2), and real time-PCR (RT-PCR). Only ECE-2 protein levels decreased significantly in NDCs in a dose-dependent manner after 15 minutes of TNF-α exposure but reverted to basal levels after 3 hours. Basal NEP gene expression levels were higher in control DCs compared to NDCs but TNF-α treatment did not significantly alter the levels of expression of any of the Aβ degrading enzymes. In conclusion, apart from a transient reduction in ECE-2 protein levels, TNF-α had no impact in our in vitro experimental system on transcription or translation of any of our selected mediators of Aβ degradation.
Dementia Research Group, School of Clinical Sciences, University of Bristol, John James Building, Frenchay Hospital Bristol, BS16 1LE, United Kingdom.
Doris
D
Culpan
Jennifer
J
Palmer
J Scott
JS
Miners
Seth
S
Love
Patrick G
PG
Kehoe