The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses.
The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses.
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DOI：
10.1186/1742-2094-11-49
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发表时间：
2014-03-19
影响因子：
9.3
通讯作者：
Yang XS
中科院分区：
文献类型：
--
作者：
He GL;Liu Y;Li M;Chen CH;Gao P;Yu ZP;Yang XS
在几种神经系统病症和疾病中普遍存在的小胶质细胞清除不足与MFG-E8表达和炎症反应错综复杂地交织在一起。电磁场（EMF）暴露可以引起促炎激活，也可能引发小胶质细胞清除功能的改变。姜黄素在抗炎和吞噬过程中具有重要作用。在这里，我们评估了姜黄素改善EMF暴露的小胶质细胞（N9细胞）的吞噬能力的能力，并记录了相关途径。N9细胞用或不用重组鼠MFG-E8（rmMFG-E8）、姜黄素和toll样受体4抗体（抗TLR 4）预处理，随后用EMF或假暴露处理。使用含磷脂酰丝氨酸的荧光生物颗粒评价它们的吞噬能力。通过CD 11b免疫反应性评估小胶质细胞的促炎活化，并通过酶联免疫吸附试验或Griess试验评估肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1 β（IL-1β）和一氧化氮（NO）的产生。通过Western blotting检测MFG-E8、αvβ3整合素、TLR 4、核因子-κB（NF-κB）和信号转导和转录激活因子3（STAT 3）的表达，评价姜黄素对电磁场暴露的N9细胞吞噬能力的影响。电磁场暴露显著增强了N9细胞CD 11b的表达，并抑制了N9细胞的吞噬能力。rmMFG-E8能明显改善N9细胞在电磁场作用下的吞噬能力。我们还发现，电磁场暴露显着增加促炎细胞因子（TNF-α，IL-6和IL-1β）的分泌和NO的产生;然而，这些增加被有效地冷却添加到培养基中的姜黄素。这种减少导致EMF暴露的N9细胞的吞噬能力的改善。Western blot分析显示姜黄素和纳洛酮恢复了MFG-E8的表达，但对TLR 4和胞浆STAT 3没有影响。姜黄素还能显著降低NF-κB B p65在细胞核中的表达以及磷酸化STAT 3（p-STAT 3）在细胞质和细胞核中的表达。本研究表明，姜黄素改善了MFG-E8表达的降低和EMF暴露的N9细胞的吞噬能力的减弱，这归因于通过NF-κB和STAT 3途径抑制促炎反应。
Insufficient clearance by microglial cells, prevalent in several neurological conditions and diseases, is intricately intertwined with MFG-E8 expression and inflammatory responses. Electromagnetic field (EMF) exposure can elicit the pro-inflammatory activation and may also trigger an alteration of the clearance function in microglial cells. Curcumin has important roles in the anti-inflammatory and phagocytic process. Here, we evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed microglial cells (N9 cells) and documented relative pathways. N9 cells were pretreated with or without recombinant murine MFG-E8 (rmMFG-E8), curcumin and an antibody of toll-like receptor 4 (anti-TLR4), and subsequently treated with EMF or a sham exposure. Their phagocytic ability was evaluated using phosphatidylserine-containing fluorescent bioparticles. The pro-inflammatory activation of microglia was assessed via CD11b immunoreactivity and the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nitric oxide (NO) via the enzyme-linked immunosorbent assay or the Griess test. We evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed N9 cells, including checking the expression of MFG-E8, αvβ3 integrin, TLR4, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) using Western blotting. EMF exposure dramatically enhanced the expression of CD11b and depressed the phagocytic ability of N9 cells. rmMFG-E8 could clearly ameliorate the phagocytic ability of N9 cells after EMF exposure. We also found that EMF exposure significantly increased the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the production of NO; however, these increases were efficiently chilled by the addition of curcumin to the culture medium. This reduction led to the amelioration of the phagocytic ability of EMF-exposed N9 cells. Western blot analysis revealed that curcumin and naloxone restored the expression of MFG-E8 but had no effect on TLR4 and cytosolic STAT3. Moreover, curcumin significantly reduced the expression of NF-κB p65 in nuclei and phospho-STAT3 (p-STAT3) in cytosols and nuclei. This study indicates that curcumin ameliorates the depressed MFG-E8 expression and the attenuated phagocytic ability of EMF-exposed N9 cells, which is attributable to the inhibition of the pro-inflammatory response through the NF-κB and STAT3 pathways.
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DOI：
10.4049/jimmunol.182.1.581
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Komura H;Miksa M;Wu R;Goyert SM;Wang P
通讯作者：
Wang P
DOI：
10.1196/annals.1332.005
发表时间：
2004-01-01
期刊：
PROTECTIVE STRATEGIES FOR NEURODEGENERATIVE DISEASES
影响因子：
--
作者：
Cole, GM;Morihara, T;Frautschy, SA
通讯作者：
Frautschy, SA
影响因子：
6.1
作者：
Jung, Ki Kyung;Lee, Hae Sung;Kang, Seog Youn
通讯作者：
Kang, Seog Youn
影响因子：
37.8
作者：
Ait-Oufella, Hafid;Kinugawa, Kiyoka;Mallat, Ziad
通讯作者：
Mallat, Ziad
影响因子：
64.8
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM