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, Byong 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
C2 - 18675783
AN - SCOPUS:49449117144
VL - 374
SP - 777
EP - 782
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -