Neuropeptide Y inhibits interleukin-1 beta-induced microglia motility
Neuropeptide Y inhibits interleukin-1 beta-induced microglia motility
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DOI：
10.1111/j.1471-4159.2011.07541.x
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发表时间：
2012-01-01
影响因子：
4.7
通讯作者：
Malva, Joao O.
中科院分区：
文献类型：
--
作者：
Ferreira, Raquel;Santos, Tiago;Malva, Joao O.
越来越多的证据表明，神经肽Y（NPY）可能是健康和疾病中大脑和免疫系统之间相互作用的关键调节剂。在本研究中，我们解剖了炎症相关的小胶质细胞运动的可能的抑制作用的NPY。通过激活Y1受体，发现NPY抑制脂多糖（LPS）诱导的小胶质细胞（N9细胞系）运动。此外，用LPS刺激小胶质细胞可被IL-1受体拮抗剂（IL-1 ra）抑制，表明内源性白细胞介素-1 β（IL-1 β）参与了这一过程。IL-1 β直接刺激促进下游p38丝裂原活化蛋白激酶的动员，并增加小胶质细胞的运动。此外，一贯的，p38丝裂原活化蛋白激酶抑制肌动蛋白丝重组的程度降低发生在质膜皱褶和p38磷酸化抑制NPY，涉及Y1受体。值得注意的是，NPY对LPS诱导的CD 11b阳性细胞运动的关键抑制作用在小鼠脑皮质外植体中得到进一步证实。总之，我们揭示了一种新的功能作用，神经肽Y在调节小胶质细胞的功能，可能有重要的意义，在调制中枢神经系统损伤/疾病，其中小胶质细胞迁移/运动可能发挥作用。
Increasing evidences suggest that neuropeptide Y (NPY) may act as a key modulator of the cross-talk between the brain and the immune system in health and disease. In the present study, we dissected the possible inhibitory role of NPY upon inflammation-associated microglial cell motility. NPY, through activation of Y1 receptors, was found to inhibit lipopolysaccharide (LPS)-induced microglia (N9 cell line) motility. Moreover, stimulation of microglia with LPS was inhibited by IL-1 receptor antagonist (IL-1ra), suggesting the involvement of endogenous interleukin-1 beta (IL-1 beta) in this process. Direct stimulation with IL-1 beta promoted downstream p38 mitogen-activated protein kinase mobilization and increased microglia motility. Moreover, consistently, p38 mitogen-activated protein kinase inhibition decreased the extent of actin filament reorganization occurring during plasma membrane ruffling and p38 phosphorylation was inhibited by NPY, involving Y1 receptors. Significantly, the key inhibitory role of NPY on LPS-induced motility of CD11b-positive cells was further confirmed in mouse brain cortex explants. In summary, we revealed a novel functional role for NPY in the regulation of microglial function that may have important implications in the modulation of CNS injuries/diseases where microglia migration/motility might play a role.