Type I interferons impair BDNF-induced cell signaling and neurotrophic activity in differentiated human SH-SY5Y neuroblastoma cells and mouse primary cortical neurons
J. Neurochem. (2012) 122, 5871. Abstract Type I interferons (IFNs) have been shown to act on neurons and to cause neuronal damage through mechanisms not completely defined. Here, we investigated the effects of type I IFNs on brain-derived neurotrophic factor (BDNF)-induced TrkB receptor signaling and neurotrophic activity. In retinoic acid-treated human SH-SY5Y neuroblastoma cells and mouse primary cortical neurons, long-term exposure to IFNs curtailed BDNF-induced activation of phosphatidylinositol 3-kinase, phospholipase C? and extracellular-regulated kinases 1 and 2 signaling. Moreover, IFN-beta inhibited BDNF-induced cell survival, neurite outgrowth, and expression of neuronal markers, such as neurofilament proteins, growth-associated protein-43 and glutamate a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluR1. The IFN inhibitory effects were associated with down-regulation of TrkB and inhibition of TrkB autophosphorylation. In SH-SY5Y cells, blockade of either Janus kinase with pyridone 6 or signal transducer and activator of transcription (STAT) 1 with siRNA transfection attenuated IFN-beta-induced TrkB down-regulation. Quantitative real time RT-PCR indicated that IFN-beta significantly reduced TrkB mRNA levels. Moreover, blockade of protein kinase R counteracted IFN-beta-induced inhibition of TrkB expression and signaling. These data indicate that in neuronal cells IFNs negatively regulate BDNF signaling and neurotrophic activity through inhibition of TrkB activation and Janus kinase/Signal transducer and activator of transcription-dependent down-regulation of TrkB.
机构:
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Christophi, George P.
;
Hudson, Chad A.
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Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Hudson, Chad A.
;
Gruber, Ross
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Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Gruber, Ross
;
Christophi, Christoforos P.
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Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Christophi, Christoforos P.
;
Massa, Paul T.
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Upstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
机构:
Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia
de Weerd, Nicole A.
;
Samarajiwa, Shamith A.
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Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia
Samarajiwa, Shamith A.
;
Hertzog, Paul J.
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Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia
机构:
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Christophi, George P.
;
Hudson, Chad A.
论文数: 0引用数: 0
h-index: 0
机构:
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Hudson, Chad A.
;
Gruber, Ross
论文数: 0引用数: 0
h-index: 0
机构:
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Gruber, Ross
;
Christophi, Christoforos P.
论文数: 0引用数: 0
h-index: 0
机构:
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Christophi, Christoforos P.
;
Massa, Paul T.
论文数: 0引用数: 0
h-index: 0
机构:
Upstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
Upstate Med Univ SUNY, Dept Microbiol & Immunol, Syracuse, NY 13210 USAUpstate Med Univ SUNY, Dept Neurol, Syracuse, NY 13210 USA
机构:
Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia
de Weerd, Nicole A.
;
Samarajiwa, Shamith A.
论文数: 0引用数: 0
h-index: 0
机构:
Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia
Samarajiwa, Shamith A.
;
Hertzog, Paul J.
论文数: 0引用数: 0
h-index: 0
机构:
Monash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, AustraliaMonash Univ, Monash Inst Med Res, Ctr Funct Genom & Human Dis, Clayton, Vic 3168, Australia