Department of Neurobiology, Third Military Medical University, Chongqing 400038, PR China.
Neurosci Lett. 2012 Oct 11;527(2):110-4. doi: 10.1016/j.neulet.2012.08.039. Epub 2012 Aug 29.
Rab GTPases have emerged as central regulators of vesicle trafficking and are essential for cytokine production during the pathogenesis of neuroinflammation. To characterize the roles of different Rab proteins in brain inflammation, we used quantitative PCR (qPCR) to examine the expression profiles of all members of the Rab family in an experimental model of brain inflammation in mice. We found that Rab20 and Rab32 were substantially up-regulated during the acute phase of inflammation. The increased expression of Rab20 was also confirmed by immunostaining of inflamed brains at different timepoints. The concomitant overexpression of Rabs (Rab20 and Rab32) and early response proinflammatory cytokines (TNF-α and IL-1β) suggested that these Rabs may be important for subsequent inflammatory responses in brain. Furthermore, we found that the expression of certain Rabs was dramatically reduced in cultured primary microglia, which was not observed in the in vivo profiling. In N9, a microglial cell line, however, there was no increase in the expression of Rab20 or Rab32, but Rab3c was significantly overexpressed. These results collectively indicate that Rabs may participate in inflammatory response in microglia during brain inflammation. The differential regulation of individual Rabs in different experimental systems is a caveat for the analysis of Rab functions.
Rab GTPases 已成为囊泡运输的核心调节剂，对于神经炎症发病过程中的细胞因子产生至关重要。为了研究不同 Rab 蛋白在脑炎症中的作用，我们使用定量 PCR（qPCR）方法在小鼠脑炎症实验模型中检测了 Rab 家族所有成员的表达谱。我们发现 Rab20 和 Rab32 在炎症急性期显著上调。Rab20 的表达增加也通过在不同时间点对炎症大脑进行免疫染色得到了证实。Rab（Rab20 和 Rab32）和早期反应促炎细胞因子（TNF-α 和 IL-1β）的同时过表达表明这些 Rab 可能对大脑中的后续炎症反应很重要。此外，我们发现培养的原代小胶质细胞中某些 Rab 的表达显著降低，但在体内分析中并未观察到这种情况。然而，在 N9 小胶质细胞系中，Rab20 或 Rab32 的表达并没有增加，而是 Rab3c 显著过表达。这些结果表明，Rab 可能参与脑炎症中小胶质细胞的炎症反应。在不同的实验系统中，个别 Rab 的差异调节是分析 Rab 功能的一个注意事项。
