Abstract:
:Pigment epithelium-derived factor (PEDF) is a potent and broadly acting neurotrophic factor that protects neurons in various types of cultured neurons against glutamate excitotoxicity and induced-apoptosis. Some of the effects of PEDF reflect specific changes in gene expression, mediated via activation of the transcription factor NF-kappa B in neurons. To investigate whether PEDF also modulates gene expression in astrocytes, we employed the use of RT-PCR to analyze the gene expression of certain pro-inflammatory genes and found that genes such as IL-1 beta, IL-6, TNF-alpha, MIP1 alpha, and MIP3 alpha were induced in PEDF-treated cultured neonatal astrocytes, but not in adult astrocytes. Electrophoresis mobility shift assay (EMSA) revealed that a time- and dose-dependent increase of NF-kappa B- and AP-1-DNA binding activity was observed in PEDF-treated neonatal astrocytes. Furthermore, rapid phosphorylation of CREB protein had occurred in PEDF-treated neonatal astrocytes. Upregulation of pro-inflammatory and AP-1-related genes by PEDF was blocked by overexpression of dominant negative CREB or a mutated form of I kappa B alpha. These results suggest that the induction of pro-inflammatory genes is mediated via activation of NF-kappa B, AP-1, and CREB in neonatal astrocytes. Taken together, these results demonstrate that PEDF is a multipotent factor, capable of affecting not only neurons, but also neonatal astrocytes, and suggests that it may act as a neuroimmune modulator in the developmental brain.
journal_name
Gliajournal_title
Gliaauthors
Yabe T,Sanagi T,Schwartz JP,Yamada Hdoi
10.1002/glia.20171subject
Has Abstractpub_date
2005-05-01 00:00:00pages
223-34issue
3eissn
0894-1491issn
1098-1136journal_volume
50pub_type
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