Inhibition of PMA-induced endothelial cell activation and adhesion by over-expression of domain negative IkappaBalpha protein

World J Gastroenterol. 2005 May 28;11(20):3080-4. doi: 10.3748/wjg.v11.i20.3080.

Abstract

Aim: NF-kappaB, regulate the expression of cytokine-inducible genes involving immune and inflammatory responses, will be potential therapy approach for allograft from rejection. In this study, we use pCMV- IkappaBalphaM vector to inhibit NF-kappaB activation and investigate the effect of pCMV- IkappaBalphaM in inhibition of T cells adhesion to endothelial cells.

Methods: The NF-kappaB activity was detected with pNF-kappaB reporter gene and electrophoretic mobility shift assay. Expression of cell surface molecules was detected by RT-PCR and flow cytometer. The cell-cell adhesion assay was performed to determine the effect of pCMV-IkappaBalphaM in inhibition of T cells adhesion to endothelial cells.

Results: We could find that NF-kappaB activity is inhibited by over-expression of non-degraded IkappaBalpha protein. Expression of adhesion molecules like ICAM-1, VCAM-1, and P-selectin as well as cell-cell adhesion were inhibited significantly by transfection of the pCMV- IkappaBalphaM vector.

Conclusion: Our results indicate that the pCMV- IkappaBalphaM, which inhibit the activity of NF-kappaB through over-expression of non-degraded IkappaBalpha protein, can be used for gene therapy in diseases involving NF-kappaB activation abnormally like organ transplantation via inhibiting cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology*
  • Endothelium, Vascular / cytology*
  • Graft Rejection / immunology
  • Humans
  • I-kappa B Proteins / biosynthesis*
  • NF-KappaB Inhibitor alpha
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • I-kappa B Proteins
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • Tetradecanoylphorbol Acetate