Pigment epithelium-derived factor induces pro-inflammatory genes in neonatal astrocytes through activation of NF-κB and CREB
✍ Scribed by Takeshi Yabe; Tomomi Sanagi; Joan P. Schwartz; Haruki Yamada
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 765 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0894-1491
No coin nor oath required. For personal study only.
✦ Synopsis
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-kB 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-1b, IL-6, TNF-a, MIP1a, and MIP3a 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-kB-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 IkBa. These results suggest that the induction of pro-inflammatory genes is mediated via activation of NF-kB, 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. V