Activation of alpha7 nicotinic acetylcholine receptor by nicotine selectively up-regulates cyclooxygenase-2 and prostaglandin E2 in rat microglial cultures.
Activation of alpha7 nicotinic acetylcholine receptor by nicotine selectively up-regulates cyclooxygenase-2 and prostaglandin E2 in rat microglial cultures.
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DOI：
10.1186/1742-2094-2-4
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发表时间：
2005-01-25
影响因子：
9.3
通讯作者：
Minghetti L
中科院分区：
文献类型：
--
作者：
De Simone R;Ajmone-Cat MA;Carnevale D;Minghetti L
烟碱乙酰胆碱 (Ach) 受体是配体门控五聚体离子通道，其主要功能是在外周和中枢神经系统中传递神经递质 Ach 的信号。然而，最近在几种非神经元细胞中发现了α7烟碱受体，并将其描述为细胞功能的重要调节剂。最近有报道称，尼古丁和乙酰胆碱可以抑制人类巨噬细胞以及小鼠小胶质细胞培养物中肿瘤坏死因子-α (TNF-α) 的产生。在本研究中，我们研究了特异性激动剂尼古丁对α7烟碱受体的刺激是否可以通过促进和/或抑制其他重要的促炎和脂质介质（例如前列腺素E2）的释放来影响活化小胶质细胞的功能状态。采用RT-PCR、免疫荧光染色和Western blot检测大鼠小胶质细胞α7烟碱受体的表达。在用尼古丁预处理的静息或脂多糖 (LPS) 刺激的小胶质细胞中分析了 α7 受体激活的功能效应。检测培养基中肿瘤坏死因子、白细胞介素-1β、一氧化氮、白细胞介素-10和前列腺素E2的水平。通过RT-PCR测定总RNA中COX-2 mRNA的表达。大鼠小胶质细胞表达α7烟碱受体，其被烟碱剂量依赖性激活可减少LPS诱导的TNF-α释放，但对一氧化氮、白细胞介素10和白细胞介素1β影响很小或没有影响。相比之下，尼古丁增强环加氧酶-2 的表达及其主要产物之一前列腺素 E2 的合成。由于前列腺素 E2 调节多种巨噬细胞和淋巴细胞功能，有助于炎症消退，因此我们的研究进一步支持了由 α7 烟碱受体介导的脑胆碱能抗炎途径的存在，该途径可用于多种神经病理学的新治疗，其中由激活的小胶质细胞维持的局部炎症发挥着至关重要的作用。 角色。
Nicotinic acetylcholine (Ach) receptors are ligand-gated pentameric ion channels whose main function is to transmit signals for the neurotransmitter Ach in peripheral and central nervous system. However, the α7 nicotinic receptor has been recently found in several non-neuronal cells and described as an important regulator of cellular function. Nicotine and ACh have been recently reported to inhibit tumor necrosis factor-α (TNF-α) production in human macrophages as well as in mouse microglial cultures. In the present study, we investigated whether the stimulation of α7 nicotinic receptor by the specific agonist nicotine could affect the functional state of activated microglia by promoting and/or inhibiting the release of other important pro-inflammatory and lipid mediator such as prostaglandin E2. Expression of α7 nicotinic receptor in rat microglial cell was examined by RT-PCR, immunofluorescence staining and Western blot. The functional effects of α7 receptor activation were analyzed in resting or lipopolysaccharide (LPS) stimulated microglial cells pre-treated with nicotine. Culture media were assayed for the levels of tumor necrosis factor, interleukin-1β, nitric oxide, interleukin-10 and prostaglandin E2. Total RNA was assayed by RT-PCR for the expression of COX-2 mRNA. Rat microglial cells express α7 nicotinic receptor, and its activation by nicotine dose-dependently reduces the LPS-induced release of TNF-α, but has little or no effect on nitric oxide, interleukin-10 and interleukin-1β. By contrast, nicotine enhances the expression of cyclooxygenase-2 and the synthesis of one of its major products, prostaglandin E2. Since prostaglandin E2 modulates several macrophage and lymphocyte functions, which are instrumental for inflammatory resolution, our study further supports the existence of a brain cholinergic anti-inflammatory pathway mediated by α7 nicotinic receptor that could be potentially exploited for novel treatments of several neuropathologies in which local inflammation, sustained by activated microglia, plays a crucial role.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
5
作者：
Clementi, F;Fornasari, D;Gotti, C
通讯作者：
Gotti, C
影响因子：
5
作者：
Conti-Fine, BM;Navaneetham, D;Maus, ADJ
通讯作者：
Maus, ADJ
影响因子：
5.1
作者：
De Simone, R;Ajmone-Cat, MA;Minghetti, L
通讯作者：
Minghetti, L
影响因子：
6.1
作者：
Banerjee, C;Nyengaard, JR;Schröder, H
通讯作者：
Schröder, H