Format

Send to

Choose Destination
Neuroimmunomodulation. 2008;15(2):117-24. doi: 10.1159/000148194. Epub 2008 Aug 5.

Gamma-aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells.

Author information

1
Department of Chemistry, University of Nevada, Las Vegas, Nevada 89154-4003, USA.

Abstract

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.

PMID:
18679050
PMCID:
PMC2859952
DOI:
10.1159/000148194
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center