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

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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.