Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells.
Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells.
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DOI：
10.1186/1742-2094-8-169
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发表时间：
2011-12-02
影响因子：
9.3
通讯作者：
Malva JO
中科院分区：
文献类型：
--
作者：
Ferreira R;Santos T;Viegas M;Cortes L;Bernardino L;Vieira OV;Malva JO
神经肽Y（NPY）是大脑和免疫系统之间通讯的调节剂。然而，尽管有越来越多的证据支持NPY在调节小胶质细胞对炎症反应中的作用，但关于NPY对小胶质细胞吞噬活性的作用（脑损伤中炎症反应的重要组成部分）没有一致的信息。考虑到这一点，我们试图评估NPY作为小胶质细胞吞噬作用的调节剂的潜在新作用。使用N9小鼠小胶质细胞系来评估NPY在吞噬作用中的作用。为此，在脂多糖（LPS）和白细胞介素-1 β（IL-1β）激发以及NPY处理的情况下进行IgG调理乳胶珠试验。随后使用NPY受体激动剂和拮抗剂的药理学方法来揭示涉及哪种NPY受体。此外，蛋白质印迹和免疫细胞化学研究进行评估的表达p38丝裂原活化蛋白激酶（MAPK）和热休克蛋白27（HSP 27），在炎症的情况下，在NPY治疗。在这里，我们表明，神经肽Y抑制吞噬作用的调理乳胶珠，抑制肌动蛋白细胞骨架重组引发的LPS刺激。用LPS和三磷酸腺苷共刺激小胶质细胞也导致吞噬作用增加，这一作用被白细胞介素-1受体拮抗剂抑制，表明IL-1β信号转导参与其中。此外，直接应用LPS或IL-1β激活下游信号分子，包括p38 MAPK和HSP 27，并且这些作用被NPY抑制。此外，我们还观察到NPY对吞噬的抑制作用是通过激活Y1受体介导的。总之，我们已经确定了一个新的作用，神经肽Y在调节小胶质细胞吞噬功能，在炎症的情况下。
Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. However, in spite of increasing evidence that supports a role for NPY in the modulation of microglial cell responses to inflammatory conditions, there is no consistent information regarding the action of NPY on microglial phagocytic activity, a vital component of the inflammatory response in brain injury. Taking this into consideration, we sought to assess a potential new role for NPY as a modulator of phagocytosis by microglial cells. The N9 murine microglial cell line was used to evaluate the role of NPY in phagocytosis. For that purpose, an IgG-opsonized latex bead assay was performed in the presence of lipopolysaccharide (LPS) and an interleukin-1β (IL-1β) challenge, and upon NPY treatment. A pharmacological approach using NPY receptor agonists and antagonists followed to uncover which NPY receptor was involved. Moreover, western blotting and immunocytochemical studies were performed to evaluate expression of p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27), in an inflammatory context, upon NPY treatment. Here, we show that NPY inhibits phagocytosis of opsonized latex beads and inhibits actin cytoskeleton reorganization triggered by LPS stimulation. Co-stimulation of microglia with LPS and adenosine triphosphate also resulted in increased phagocytosis, an effect inhibited by an interleukin-1 receptor antagonist, suggesting involvement of IL-1β signaling. Furthermore, direct application of LPS or IL-1β activated downstream signaling molecules, including p38 MAPK and HSP27, and these effects were inhibited by NPY. Moreover, we also observed that the inhibitory effect of NPY on phagocytosis was mediated via Y1 receptor activation. Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
3.3
作者：
Bedoui, Sammy;Kromer, Andreas;von Hoersten, Stephan
通讯作者：
von Hoersten, Stephan
影响因子：
2.4
作者：
Gregory, DJ;Olivier, M
通讯作者：
Olivier, M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3
作者：
Bedoui, Sammy;von Hoersten, Stephan;Gebhardt, Thomas
通讯作者：
Gebhardt, Thomas