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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Astrocytoma / genetics*
  • Astrocytoma / immunology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / immunology*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • I-kappa B Proteins / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • NF-KappaB Inhibitor alpha
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / immunology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Tumor Necrosis Factor-alpha / pharmacology
  • gamma-Aminobutyric Acid / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • I-kappa B Proteins
  • Interleukin-1beta
  • Interleukin-6
  • Nfkbia protein, rat
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • gamma-Aminobutyric Acid
  • p38 Mitogen-Activated Protein Kinases