Regulatory mechanism of TNFα autoregulation in HaCaT cells: The role of the transcription factor EGR-1

Sang Wook Son, Byong Wook Min, Yoongho Lim, Young Han Lee, Soon Young Shin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine involved in innate immune response, as well as in the pathogenesis of many inflammatory diseases. Although several response elements in the TNFα promoter region are involved in the activation of gene transcription, few studies have examined the regulatory mechanism that controls TNFα autoregulation. In this study, we investigated the role of the Early Growth Response-1 (EGR-1) transcription factor in TNFα autoregulation in HaCaT human keratinocytes. The requirement for EGR-1 in TNFα autoregulation was confirmed using a construct harboring a point mutation in the EGR-1 binding site within the TNFα promoter and the introduction of EGR-1 siRNA. Inhibition of the ERK or JNK pathway suppressed TNFα-induced EGR-1 expression, resulting in the inhibition of TNFα-induced TNFα promoter activation. These results reveal that the ERK and JNK MAPK pathways contribute to the autoregulation of TNFα synthesis via EGR-1 induction in HaCaT keratinocytes.

Original languageEnglish
Pages (from-to)777-782
Number of pages6
JournalBiochemical and biophysical research communications
Volume374
Issue number4
DOIs
Publication statusPublished - 2008 Oct 3

Keywords

  • Autoregulation
  • EGR-1
  • Mitogen-activated protein kinase
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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