School of Preclinical Medicine, Beijing University of Chinese Medicine, Chao Yang District, China.
Brain Res Bull. 2011 Aug 10;86(1-2):53-9. doi: 10.1016/j.brainresbull.2011.06.016. Epub 2011 Jul 2.
Neuronal survival can be influenced by activated microglia, but limited evidence exists on the effects of paracrine signaling from brain microvascular endothelial cells (BMECs) on microglial action. Therefore, we examined the effects of normal BMECs conditioned medium (BMECs-CM) on activated microglia induced by pro-inflammatory cytokine macrophage inflammatory protein-1beta (MIP-1β), a chemokine that released from ischemic BMECs and has been proved to stimulate microglial proliferation. Our results showed that BMECs-CM inhibited the proliferation and transmigration of microglia induced by MIP-1β. Moreover, BMECs-CM significantly suppressed the expression of the MIP-1β receptor, CCR5, and the phosphorylation of p38 and JNK (P<0.05). These findings suggest that BMECs-CM could inhibit MIP-1β-induced microglial activation. Future therapeutic strategies that prioritize the early recovery of BMECs could be beneficial for microglial inhibition and further increase neuronal survival.
神经元的存活可以受到激活的小胶质细胞的影响，但是关于脑微血管内皮细胞（BMEC）的旁分泌信号对小胶质细胞作用的影响的证据有限。因此，我们研究了正常 BMEC 条件培养基（BMEC-CM）对由促炎细胞因子巨噬细胞炎性蛋白-1β（MIP-1β）诱导的激活的小胶质细胞的影响，MIP-1β 是一种趋化因子，可从缺血性 BMEC 中释放，并已被证明可刺激小胶质细胞增殖。我们的结果表明，BMEC-CM 抑制了 MIP-1β 诱导的小胶质细胞的增殖和迁移。此外，BMEC-CM 还显著抑制了 MIP-1β 受体 CCR5 的表达以及 p38 和 JNK 的磷酸化（P<0.05）。这些发现表明，BMEC-CM 可以抑制 MIP-1β 诱导的小胶质细胞激活。优先重视早期恢复 BMEC 的未来治疗策略可能有利于抑制小胶质细胞并进一步增加神经元的存活。
