Gamma-aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells.
Gamma-aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells.
复制标题
γ-氨基丁酸抑制星形细胞瘤细胞中白细胞介素 6 的协同释放，但不抑制转录激活。
DOI：
10.1159/000148194
复制
发表时间：
2008
影响因子：
2.4
通讯作者：
Spangelo,BryanL
中科院分区：
文献类型：
--
作者：
RoachJr,JosephD;Aguinaldo,GrantT;Jonnalagadda,Kaumudi;HughesJr,FrancisM;Spangelo,BryanL
目的：抑制性神经递质γ-氨基丁酸（γ-aminobutyric acid，GABA）的减少可能促进阿尔茨海默病（Alzheimer 'sdisease，AD）中细胞因子的释放，导致神经炎症。方法：在GABA存在和不存在的情况下，用IL-1 β和TNF-α处理大鼠C6星形细胞瘤细胞，观察GABA对IL-1β和TNF-α协同释放IL-6的抑制作用。Western blot检测p38的活化、IL-6的降解和IL-6的表达。结果：虽然p38和核因子（NF）-κ B是IL-6协同释放的必要条件，但GABA对p38磷酸化和NF-κ B-α降解均无影响。此外，GABA抑制IL-6释放，但不改变IL-6基因表达的马槟榔驱动的协同增加。Western blot分析显示，IL-1β和TNF-α联合作用可导致细胞内IL-6的增加，而GABA可阻止这种增加。结论：GABA抑制IL-6的释放与细胞内IL-6的减少是一致的。GABA诱导的IL-6释放的抑制可能包括IL-6基因翻译的抑制。
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.