Overexpression of S100A7 Protects LPS-Induced Mitochondrial Dysfunction and Stimulates IL-6 and IL-8 in HaCaT Cells

作者：Wenyan Sun, Yan Zheng, Zhuoyang Lu, Yang Cui, Qiong Tian, Shengxiang Xiao, Feng Liu, Jiankang Liu · 发表于：PLoS ONE · 年份：2014 · DOI：10.1371/journal.pone.0092927 · 被引用次数：13 · 研究领域：S100 Proteins and Annexins、Inflammasome and immune disorders、Advanced Glycation End Products research

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 ...