title: Caveolin-1, through its ability to negatively regulate TLR4, is a crucial determinant of MAPK activation in LPS-challenged mammary epithelial cells.
abstract: BACKGROUND
  To explore the role of caveolin-1(CAV-1) gene silencing on MAPK activation in lipopolysaccharide (LPS)-challenged human mammary epithelial cells.
  
  
  METHODS
  We established a MCF-10ACE of CAV-1 gene silencing from human mammary epithelial cell line MCF-10A by RNAi technology. DNA Microarray were used to detect the expression of inflammation-associated genes in MCF-10ACE. Western blotting was used to examine the activation of MAPK in lipopolysaccharide(LPS)-challenged MCF-10A and MCF-10ACE. Moreover, immunofluorescence and Western bloting were performed to detect the co-localization of CAV-1 and toll-like receptor 4 (TLR4) in human mammary epithelial cells.
  
  
  RESULTS
  MCF-10ACE exhibited significant increases in inflammation-associated gene expression, especially IL-6 (~7-fold) and IL6R (~17-fold). In addition, LPS-induced p38 MAPK and JNK MAPK activation was significantly increased in MCF-10ACE. Furthermore, CAV-1 co- localized with TLR4 and appeared a negative correlation trend.
  
  
  CONCLUSIONS
  CAV-1 gene silencing promotes MAPK activation via TLR4 signaling in human mammary epithelial cells response to LPS.
authors.affiliation: College of Life Sciences, Liaoning Normal University, Dalian, Liaoning, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Huang
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases