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Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells.

Abstract：

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 α (TNFα) 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 μM and 30 μM. 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-IκB 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.

journal_name

J Affect Disord

journal_title

Journal of affective disorders

authors

Hongxia L,Yuxiao T,Zhilei S,Yan S,Yicui Q,Jiamin S,Xin X,Jianxin Y,Fengfeng M,Hui S

doi

10.1016/j.jad.2019.02.041

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

136-142

eissn

0165-0327

issn

1573-2517

pii

S0165-0327(18)32402-9

journal_volume

249

pub_type

杂志文章

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