title: Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and stimulates IL-6 and IL-8 in HaCaT cells.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Dermatology, the 2nd Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Zhuoyang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Dermatology, the 2nd Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Dermatology, the 2nd Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P. R. China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Medicine, University of California Irvine Medical School, Irvine, United States of America; Chao Family Comprehensive Cancer Center, University of California Irvine Medical School, Irvine, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China; Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, United States of America.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D004272:DNA, Mitochondrial / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D001678:Organelle Biogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004272:DNA, Mitochondrial; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human