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.