Caveolin-1, through its ability to negatively regulate TLR4, is a crucial determinant of MAPK activation in LPS-challenged mammary epithelial cells

Asian Pac J Cancer Prev. 2013;14(4):2295-9. doi: 10.7314/apjcp.2013.14.4.2295.

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.

Conclusion: CAV-1 gene silencing promotes MAPK activation via TLR4 signaling in human mammary epithelial cells response to LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Blotting, Western
  • Caveolin 1 / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Interleukin-6 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / drug effects
  • Mammary Glands, Human / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Biomarkers
  • Caveolin 1
  • Interleukin-6
  • Lipopolysaccharides
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases