Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its...

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Tumor necrosis factor-alpha (TNF-α) is a cytokine with diverse biological activities.
• Astrocytes, a type of glial cell, express glial fibrillary acidic protein (GFAP) as an intermediate filament component.
• Previous studies suggested TNF-α may be mitogenic to astrocytes.

Purpose of the Study:

• To investigate the effect of TNF-α on GFAP expression in primary astrocytes and U373 glioblastoma cells.
• To examine TNF-α's impact on interleukin-6 (IL-6) expression in astrocytes.
• To determine if TNF-α affects cell proliferation and total protein content.

Main Methods:

• Primary neonatal astrocytes and U373 glioblastoma cells were treated with TNF-α for 72 hours.
• GFAP and IL-6 expression levels were measured.
• Cell proliferation was assessed using thymidine uptake assays.
• Total cellular protein content was quantified.

Main Results:

• TNF-α treatment decreased GFAP content and its encoding mRNA in both cell types.
• Astrocytes showed increased IL-6 expression following TNF-α treatment.
• U373 cells proliferated in response to TNF-α, but primary astrocytes did not.
• TNF-α increased total cellular protein content in both cell types.
• The decrease in GFAP was more pronounced in subconfluent than confluent cells.
• Basic fibroblast growth factor (bFGF) also decreased GFAP and increased total protein, indicating a non-specific effect.

Conclusions:

• TNF-α downregulates GFAP expression in astrocytes and glioblastoma cells, likely due to dilution by newly synthesized proteins.
• TNF-α stimulates IL-6 production in astrocytes.
• The observed changes in GFAP and total protein are not exclusive to TNF-α, as bFGF elicits similar effects.
• These findings highlight TNF-α's complex role in modulating astrocyte phenotype and protein expression.