Identification of TNF-alpha-responsive NF-kappaB p65-binding element in the distal promoter of the mouse serine protease inhibitor SerpinE2

FEBS Lett. 2006 May 29;580(13):3257-62. doi: 10.1016/j.febslet.2006.04.086. Epub 2006 May 6.


Serine protease inhibitor SerpinE2 is known as a cytokine-inducible gene. Here, we investigated whether tumor necrosis factor alpha-(TNF-alpha)-induced expression of SerpinE2 is mediated by the nuclear factor-kappaB (NF-kappaB) p65 subunit. Both steady state and TNF-alpha-induced expression of SerpinE2 mRNA were abrogated in p65-/- murine embryonic fibroblasts (MEFs). Reconstitution with wild-type p65 rescued SerpinE2 mRNA expression in an IkappaB kinase beta-dependent manner. Electrophoresis mobility shift assay and ChIP assay demonstrated that p65 bound to the kappaB-like DNA sequence located at approximately -9 kbp in the SerpinE2 promoter. In addition, TNF-alpha stimulated luciferase gene expression driven by the kappaB-like element in the reconstituted MEFs, but not in p65-/- MEFs. These results indicated that activation of NF-kappaB p65 plays an important role in TNF-alpha-induced expression of SerpinE2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Nucleus
  • Fibroblasts / drug effects
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression / physiology
  • I-kappa B Kinase / antagonists & inhibitors
  • Mice
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • Protein Transport
  • RNA, Messenger / metabolism
  • Response Elements / drug effects
  • Response Elements / genetics
  • Response Elements / physiology*
  • Serpin E2
  • Serpins / genetics*
  • Thiophenes / pharmacology
  • Transcription Factor RelA / metabolism*
  • Transcriptional Activation*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*


  • RNA, Messenger
  • SC 514
  • Serpin E2
  • Serpine2 protein, mouse
  • Serpins
  • Thiophenes
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase