Gamma-aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells.
Journal Article (Journal Article)
OBJECTIVE: A decline in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may enhance cytokine release in Alzheimer's disease (AD) resulting in neuroinflammation. We investigated the GABA-mediated suppression of the synergistic release of interleukin (IL)-6 due to interleukin 1-beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). METHODS: Rat C6 astrocytoma cells were treated with IL-1 beta and TNF-alpha in the absence and presence of GABA. Activation of p38, degradation of I kappaB-alpha and total cellular IL-6 were determined by Western blot analysis. IL-6 release and gene expression were measured by ELISA and RT-PCR, respectively. RESULTS: Although p38 and nuclear factor (NF)-kappaB are essential for the synergistic release of IL-6, GABA did not affect either p38 phosphorylation or I kappaB-alpha degradation. Additionally, GABA suppressed IL-6 release but did not alter cytokine-driven synergistic increases in IL-6 gene expression. Western blot analysis revealed that co-treatments with IL-1 beta and TNF-alpha resulted in an increase in intracellular IL-6 that was prevented by GABA. CONCLUSION: GABA-induced inhibition of IL-6 release appears to coincide with a reduction in cellular IL-6. The GABA-induced suppression of IL-6 release may include inhibition of IL-6 gene translation.
Full Text
Duke Authors
Cited Authors
- Roach, JD; Aguinaldo, GT; Jonnalagadda, K; Hughes, FM; Spangelo, BL
Published Date
- 2008
Published In
Volume / Issue
- 15 / 2
Start / End Page
- 117 - 124
PubMed ID
- 18679050
Pubmed Central ID
- PMC2859952
Electronic International Standard Serial Number (EISSN)
- 1423-0216
Digital Object Identifier (DOI)
- 10.1159/000148194
Language
- eng
Conference Location
- Switzerland