Objective: A decline in the inhibitory neurotransmitter γ-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-β (IL-1β) and tumor necrosis factor-α (TNF-α). Methods: Rat C6 astrocytoma cells were treated with IL-1β and TNF-α in the absence and presence of GABA. Activation of p38, degradation of IĸB-α 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)-ĸB are essential for the synergistic release of IL-6, GABA did not affect either p38 phosphorylation or IĸB-α 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-1β and TNF-α 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.

Keywords:
Alzheimer disease, GABA, IL-1β, IL-6, TNF-α
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© 2008 S. Karger AG, Basel
2008
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