Regulatory mechanism of TNFα autoregulation in HaCaT cells

The role of the transcription factor EGR-1

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

Research output: Contribution to journalArticle

13 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

Fingerprint

Early Growth Response Protein 1
Homeostasis
Tumor Necrosis Factor-alpha
MAP Kinase Signaling System
Growth
Keratinocytes
Transcriptional Activation
Chemical activation
Response Elements
Transcription
Point Mutation
Innate Immunity
Genetic Promoter Regions
Small Interfering RNA

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Regulatory mechanism of TNFα autoregulation in HaCaT cells : The role of the transcription factor EGR-1. / Son, Sang Wook; Min, Byung Wook; Lim, Yoongho; Lee, Young Han; Shin, Soon Young.

In: Biochemical and Biophysical Research Communications, Vol. 374, No. 4, 03.10.2008, p. 777-782.

Research output: Contribution to journalArticle

@article{a48c10d043f94b978414f785a03bf300,
title = "Regulatory mechanism of TNFα autoregulation in HaCaT cells: The role of the transcription factor EGR-1",
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.",
keywords = "Autoregulation, EGR-1, Mitogen-activated protein kinase, Tumor necrosis factor α",
author = "Son, {Sang Wook} and Min, {Byung Wook} and Yoongho Lim and Lee, {Young Han} and Shin, {Soon Young}",
year = "2008",
month = "10",
day = "3",
doi = "10.1016/j.bbrc.2008.07.117",
language = "English",
volume = "374",
pages = "777--782",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "4",

}

TY - JOUR

T1 - Regulatory mechanism of TNFα autoregulation in HaCaT cells

T2 - The role of the transcription factor EGR-1

AU - Son, Sang Wook

AU - Min, Byung Wook

AU - Lim, Yoongho

AU - Lee, Young Han

AU - Shin, Soon Young

PY - 2008/10/3

Y1 - 2008/10/3

N2 - 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.

AB - 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.

KW - Autoregulation

KW - EGR-1

KW - Mitogen-activated protein kinase

KW - Tumor necrosis factor α

UR - http://www.scopus.com/inward/record.url?scp=49449117144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49449117144&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.07.117

DO - 10.1016/j.bbrc.2008.07.117

M3 - Article

VL - 374

SP - 777

EP - 782

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 4

ER -