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


  • eng

Conference Location

  • Switzerland