Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells
Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells
复制标题
锌通过上调小胶质细胞 BV2 细胞中 A20 的表达来抑制 LPS 诱导的炎症反应
DOI：
10.1016/j.jad.2019.02.041
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发表时间：
2019-04-15
影响因子：
6.6
通讯作者：
Shen Hui
中科院分区：
文献类型：
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作者：
Li Hongxia;Tang Yuxiao;Shen Hui
背景资料：我们前期的研究已经证明补锌能有效缓解小鼠的抑郁症状，但其作用机制尚不清楚。神经炎症被认为是抑郁症发病机制中的一个重要方面。为探讨锌在神经炎症中的作用，本研究观察了锌对脂多糖（lipopolysaccharide，LPS）诱导的中枢神经系统天然免疫细胞BV 2小胶质细胞炎症反应的影响。结果：LPS处理后，海马细胞CD 11b、诱导型一氧化氮合酶（iNOS）、环氧合酶2（COX 2）、肿瘤坏死因子α（TNF α）、白细胞介素6（IL 6）的表达及活性氧（ROS）水平均明显升高。锌在10 μ M和30 μ M浓度下均能阻断ROS的产生并降低上述炎性细胞因子的表达。此外，锌干预BV 2细胞可提高BV 2细胞培养液培养的海马HT-22细胞的存活率。此外，锌指蛋白A20（一种抗炎因子）在补锌后升高，而p65、p-I κ B和p-p65水平显著降低。局限性：需要更多令人信服的证据来确保A20在锌的抗炎作用中的作用。目前的结果表明，锌抑制炎症反应介导的小胶质细胞通过上调锌指A20。有人提出，这种抗炎作用可能是以前观察到的锌的抗抑郁作用的潜在机制。
Background: Our previous studies have proved that zinc supplement effectively alleviate depression symptoms in mice, but the mechanisms are still uncertain. Neuroinflammation is considered as an important aspect in pathogenesis of depression. To elucidate the role of zinc on neuroinflammation, in this study, we investigated effects of zinc on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system.Methods: BV2 cells were treated by 100 ng/ml LPS to induce inflammatory responses and the effects of zinc sulfate (ZnSO4) addition on LPS-induced inflammation were observed. Besides, through culturing HT-22 hippocampus cells by using medium transferred from zinc-intervened BV2 cells, the protective roles of zinc on hippocampus cells were identified.Results: LPS treatment up-regulated expressions of CD11b, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) and level of reactive oxygen species (ROS). Meaningfully, zinc was capable of blocking ROS generation and reducing expressions of the above inflammatory cytokines at both 10 mu M and 30 mu M. In addition, it was proved that zinc intervention to BV2 cells could increase the viabilities of hippocampal HT-22 cells cultured by medium of BV2 cells. Furthermore, the zinc-finger protein A20, an anti-inflammation factor, was increased by zinc supplement, while levels of p65, p-I kappa B and p-p65 were significantly decreased.Limitations: More compelling proofs were needed to ensure roles of A20 in anti-inflammatory effects of zinc.Conclusions: The present results suggested that zinc inhibits inflammatory responses mediated by microglia cells via upregulation of zinc-finger A20. It was proposed that this anti-inflammatory action might be underlying mechanism of previously observed anti-depressive effects of zinc.