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Caveolin-1, Through its Ability to Negatively Regulate TLR4, is a Crucial Determinant of MAPK Activation in LPS-challenged Mammary Epithelial Cells

  • Wang, Xiao-Xi (College of Life Sciences, Liaoning Normal University) ;
  • Wu, Zheng (College of Life Sciences, Liaoning Normal University) ;
  • Huang, Hui-Fang (College of Life Sciences, Liaoning Normal University) ;
  • Han, Chao (The First Affiliated Hospital, Dalian Medical University) ;
  • Zou, Wei (College of Life Sciences, Liaoning Normal University) ;
  • Liu, Jing (The First Affiliated Hospital, Dalian Medical University)
  • Published : 2013.04.30

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 MCF10ACE. 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.

Keywords

References

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