Impact of paracrine signals from brain microvascular endothelial cells on microglial proliferation and migration

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.