Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and stimulates IL-6 and IL-8 in HaCaT cells.
Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and stimulates IL-6 and IL-8 in HaCaT cells.
复制标题
S100A7 的过表达可保护 LPS 诱导的线粒体功能障碍并刺激 HaCaT 细胞中的 IL-6 和 IL-8
DOI：
10.1371/journal.pone.0092927
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Sun W;Zheng Y;Lu Z;Cui Y;Tian Q;Xiao S;Liu F;Liu J
背景：S100A7(又称银屑病蛋白)广泛分布于正常人表皮角质形成细胞的胞浆中，在多种表皮炎症性疾病中呈高表达。内毒素诱导线粒体功能改变，在包括炎症在内的多种细胞机制中发挥重要作用。虽然S100A7在炎症过程中在人表皮中的表达受到多种因素的调节，但S100A7是否与角质形成细胞中的线粒体相互作用尚不清楚。目的探讨S100A7对脂多糖诱导的正常HaCaT细胞线粒体功能障碍的抑制作用及对细胞因子的刺激作用。结果建立了表达增强型绿色荧光蛋白(EGFP)的HaCaT细胞S100A7(S100A7-EGFP)或单独表达EGFP的HaCaT细胞作为对照。在这里，我们发现S100A7-EGFP HaCaT细胞表现出线粒体DNA(MtDNA)拷贝数和线粒体膜电位(MMP)的增加。定量逆转录聚合酶链式反应显示与线粒体生物发生相关的三个主要基因：PPAR-辅活化子-1α(pgc-1α)、线粒体转录因子A(Tfam)和核呼吸因子-1(Nrf1)的表达显著增加。S100A7的过表达增加了线粒体DNA的含量，有效地增加了细胞内三磷酸腺苷(ATP)的产生，同时减少了活性氧(ROS)的产生。与对照EGFP细胞相比，S100A7过表达还显著降低了Mfn2的表达，增加了Drp1的表达。S100A7下调自噬相关蛋白Beclin-1和LC3B的表达。S100A7还可增加IL-6和IL-8细胞因子的表达。S100A7基因敲除可降低线粒体膜电位，破坏线粒体动态平衡。结论S100A7可促进内毒素诱导的HaCaT细胞线粒体生物合成，增强线粒体功能，并促进IL-6和IL-8的分泌。
Background S100A7 (or psoriasin) is distributed in the cytoplasm of keratinocytes of normal human epidermis, and it is overexpressed in many epidermal inflammatory diseases. Lipopolysaccharide (LPS) induces mitochondrial function changes, which play important roles in multiple cellular mechanisms including inflammation. Although S100A7 expression is regulated by various factors in the human epidermis during inflammation, whether S100A7 interacts with mitochondria in keratinocytes is not clear. Objectives Our study was designed to investigate whether S100A7 could prohibit mitochondrial dysfunction and stimulate cytokines in cultured normal HaCaT cells treated with LPS. Results We generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP)-S100A7 (S100A7-EGFP) or EGFP alone, as a control. Here, we show that S100A7-EGFP HaCaT cells exhibit an increase in mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP). qRT-PCR revealed that expression of three main mitochondrial biogenesis-associated genes was significantly increased: PPAR-coactivator-1alpha (PGC-1α), the mitochondrial transcription factor A (Tfam) and nuclear respiratory factor-1 (NRF1). S100A7 overexpression increased mtDNA content and effectively increased intracellular adenosine 5′-triphosphate (ATP) production, while decreasing reactive oxygen species (ROS) generation. S100A7 overexpression also significantly decreased the expression of Mfn2 and increased DRP1 expression compared with control EGFP cells. S100A7 down-regulated the expression of the autophagy-related proteins Beclin-1 and LC3B. S100A7 also increased expression of IL-6 and IL-8 cytokines. Knockdown of S100A7 decreased MMP and disrupted mitochondrial homeostasis. Conclusions These findings demonstrate that S100A7 stimulates mitochondrial biogenesis and increases mitochondrial function in HaCaT cells treated with LPS; and S100A7 also promotes secretion of IL-6 and IL-8.
登录
查看更多内容
影响因子：
2.9
作者：
Li, XQ;de Leeuw, E;Lu, WY
通讯作者：
Lu, WY
DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Green DR;Galluzzi L;Kroemer G
通讯作者：
Kroemer G
影响因子：
3.2
作者：
Broome, AM;Ryan, D;Eckert, RL
通讯作者：
Eckert, RL
影响因子：
6.5
作者：
HOFFMANN, HJ;OLSEN, E;CELIS, JE
通讯作者：
CELIS, JE
影响因子：
11.2
作者：
Ranger JJ;Levy DE;Shahalizadeh S;Hallett M;Muller WJ
通讯作者：
Muller WJ