Autotaxin downregulates LPS-induced microglia activation and pro-inflammatory cytokines production.
Autotaxin downregulates LPS-induced microglia activation and pro-inflammatory cytokines production.
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DOI：
10.1002/jcb.24889
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发表时间：
2014-12
影响因子：
4
通讯作者：
d'Hellencourt, Christian Lefebvre
中科院分区：
文献类型：
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作者：
Awada, Rana;Saulnier-Blache, Jean Sebastien;Gres, Sandra;Bourdon, Emmanuel;Rondeau, Philippe;Parimisetty, Avinash;Orihuela, Ruben;Harry, G. Jean;d'Hellencourt, Christian Lefebvre
炎症对于防御感染或损伤至关重要。它受到严格监管，因为过度反应可能是有害的，特别是在中枢神经系统 (CNS) 等免疫特权器官中。小胶质细胞是炎症因子的主要来源，但也参与炎症的调节和修复。自分泌运动因子 (ATX) 是一种磷脂酶 D，可将溶血磷脂酰胆碱转化为溶血磷脂酸 (LPA)，并在多种中枢神经系统损伤中表达上调。 LPA 是一种多效性免疫调节因子，可以诱导多种细胞过程，包括形态变化、增殖、死亡和存活。我们模拟革兰氏阴性菌感染，研究了 ATX 对小胶质细胞脂多糖 (LPS) 炎症反应的影响。用 LPS 处理小鼠 BV-2 小胶质细胞和稳定转染、过表达 ATX-BV-2 (A+) 小胶质细胞。分别通过 qRT-PCR 和 ELISA 检查肿瘤坏死因子 α (TNFα)、白细胞介素 (IL)-6 和 IL-10 mRNA 和蛋白水平。通过放射酶测定对分泌的 LPA 进行定量，并通过流式细胞术测定小胶质细胞活化标记物（CD11b、CD14、B7.1 和 B7.2）。 LPS 处理的 BV-2 细胞中 ATX 表达和 LPA 产生显着增强。 A+细胞中LPS诱导的TNFα和IL-6的mRNA和蛋白水平受到抑制，而IL-10则增加。 A+ 细胞中 CD11b、CD14、B7.1 和 B7.2 表达减少。我们的结果强烈表明小胶质细胞失活和 ATX 的 IL-10 抑制与 LPS 诱导小胶质细胞激活。
Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death and survival. We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1 and B7.2) were determined by flow cytometry. ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1 and B7.2 expressions were reduced in A+ cells. Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation.
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影响因子：
7.4
作者：
Awada, Rana;Rondeau, Philippe;Bourdon, Emmanuel
通讯作者：
Bourdon, Emmanuel
影响因子：
5.7
作者：
Fan, Hongkuan;Zingarelli, Basilia;Cook, James A.
通讯作者：
Cook, James A.
影响因子：
4.8
作者：
Möller, T;Contos, JJ;Ransom, BR
通讯作者：
Ransom, BR
影响因子：
4.7
作者：
Ma, Lin;Nagai, Jun;Ueda, Hiroshi
通讯作者：
Ueda, Hiroshi
DOI：
10.1038/nri3071
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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