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 language | English |
|---|---|
| Pages (from-to) | 777-782 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 374 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2008 Oct 3 |
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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 journal › Article
}
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
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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 -