Type I interferons upregulate p75 neurotrophin receptor expression and signaling in human neuroblastoma cells.
DEDONI, SIMONA;OLIANAS, MARIA CONCETTA;ONALI, PIER LUIGI
2012-01-01
Abstract
The administration of type I interferon (IFN)-α and IFN-β is known to cause several neuropsychiatric side effects, such as depression, psychosis and cognitive dysfunctions. We have recently reported that long-term exposure to IFN-β induces neuronal apoptosis through activation of janus kinase-signal transducer and activator of transcription signaling and inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Moreover, we have shown that in neuronal cells IFN-β treatment impairs brain-derived neurotrophic factor (BDNF) signaling and neurotrophic activity by down-regulating the expression and activation of the BDNF receptor TrkB. In the present study we investigated the effects of IFN-β on p75 neurotrophin receptor (p75NTR), which, in addition to Trk, mediates the cellular responses to neurotrophins and pro-neurotrophins. In retinoic acid-differentiated human SH-SY5Y cells, prolonged treatment with IFN-β enhanced the stimulation of Jun N-terminal kinase phosphorylation elicited by either nerve growth factor (NGF) or pro-NGF. In addition, IFN-β exposure induced a time-dependent increase in the expression of p75NTR. These data indicate that IFN-β affects TrkB and p75NTR expression and signaling in an opposite manner, thus altering the life and death signals triggered by neurotrophins.Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.