RESUMO
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.
Assuntos
Astrocitoma/genética , Astrocitoma/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Interleucina-6/genética , Ácido gama-Aminobutírico/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Astrócitos/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Proteínas I-kappa B/metabolismo , Interleucina-1beta/farmacologia , Interleucina-6/metabolismo , Inibidor de NF-kappaB alfa , Fosforilação/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Biossíntese de Proteínas/imunologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The first examples of unsymmetrical olefin cross-metathesis reactions in water, involving water-insoluble substrates, at room temperature and using commercially available catalysts are reported. The key to success is to include small percentages of the nonionic, vitamin E-based amphiphile "PTS". The nanometer micelles formed accommodate water-insoluble substrates, along with a readily available Ru-based metathesis catalyst. Reactions proceed at ambient temperatures with high efficiency and very high E-selectivity, and products are easily isolated.
