Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China.
Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua 321000, China.
Life Sci. 2020 Sep 1;256:117894. doi: 10.1016/j.lfs.2020.117894. Epub 2020 Jun 3.
Pathological alterations in the brain can cause microglial activation (MA). Thus, inhibiting MA could provide a new approach for treating neurodegenerative disorders.
To investigate the effect of C16 peptide and angiopoietin-1 (Ang1) on inflammation following MA, we stimulated microglial BV-2 cells with lipopolysaccharide (LPS) and used dexmedetomidine (DEX) as a positive control. Specific inhibitors of Tie2, αvβ3 and α5β1 integrins, and PI3K/Akt were applied to investigate the neuron-protective and anti-inflammatory effects and signaling pathway of C16 + Ang1 treatment in the LPS-induced BV-2 cells.
Our results showed that C16 + Ang1 treatment reduced the microglia M1 phenotype but promoted the microglia M2 phenotype. In addition, C16 + Ang1 treatment suppressed leukocyte migration across human pulmonary microvascular endothelial cells, reduced the levels of pro-inflammatory factors [inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, tumor necrosis factor (TNF-α)], and cellular apoptosis factors (caspase-3 and p53), and decreased lactate dehydrogenase (LDH) release, but promoted anti-inflammatory cytokine (IL-10) expression and cell proliferation in the LPS-activated BV-2 cells. The signaling pathways underlying the neuron-protective and anti-inflammatory effects of C16 + Ang1 may be mediated by Tie2-PI3K/Akt, Tie2-integrin and integrin-PI3K/Akt.
The neuron-protective and anti-inflammatory effects of C16 + Ang1 treatment included M1 to M2 microglia phenotype switching, blocking leukocyte transmigration, decreasing apoptotic and inflammatory factors, and promoting cellular viability.
大脑中的病变会引起小胶质细胞激活（MA）。因此，抑制 MA 可能为治疗神经退行性疾病提供新的方法。
为了研究 C16 肽和血管生成素-1（Ang1）对 MA 后炎症的影响，我们用脂多糖（LPS）刺激小胶质细胞 BV-2 细胞，并将右美托咪定（DEX）作为阳性对照。我们应用 Tie2、αvβ3 和 α5β1 整合素的特异性抑制剂以及 PI3K/Akt 来研究 C16+Ang1 处理在 LPS 诱导的 BV-2 细胞中的神经保护和抗炎作用及其信号通路。
我们的结果表明，C16+Ang1 处理减少了小胶质细胞 M1 表型，但促进了小胶质细胞 M2 表型。此外，C16+Ang1 处理抑制白细胞穿过人肺微血管内皮细胞迁移，降低促炎因子[诱导型一氧化氮合酶（iNOS）、白细胞介素（IL）-1β、肿瘤坏死因子（TNF-α）]和细胞凋亡因子（caspase-3 和 p53）的水平，并减少乳酸脱氢酶（LDH）释放，但促进 LPS 激活的 BV-2 细胞中抗炎细胞因子（IL-10）的表达和细胞增殖。C16+Ang1 的神经保护和抗炎作用的信号通路可能通过 Tie2-PI3K/Akt、Tie2-整合素和整合素-PI3K/Akt 介导。
C16+Ang1 处理的神经保护和抗炎作用包括 M1 到 M2 小胶质细胞表型转换、阻断白细胞迁移、减少凋亡和炎症因子、促进细胞活力。
