TY - JOUR
T1 - Redox-regulated mechanisms of IL-4-induced MCP-1 expression in human vascular endothelial cells
AU - Lee, Yong Woo
AU - Hennig, Bernhard
AU - Toborek, Michal
PY - 2003/1/1
Y1 - 2003/1/1
N2 - The present study focused on the molecular signaling pathways of monocyte chemoattractant protein-1 (MCP-1) induction by interleukin-4 (IL-4) in human umbilical vein endothelial cells (HUVEC). RT-PCR showed that MCP-1 mRNA accumulation was markedly increased in IL-4-treated HUVEC in a time- and dose-dependent manner. Antioxidants, such as pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC), significantly inhibited IL-4-induced MCP-1 mRNA expression. These effects correlated well with the PDTC-mediated inhibition of MCP-1 promoter transcriptional activity observed in IL-4-treated HUVEC. IL-4-induced MCP-1 gene expression was paralleled by a concomitant production of MCP-1 protein. In agreement with MCP-1 gene expression, PDTC attenuated IL-4-mediated induction of MCP-1 protein expression. In addition, IL-4 dramatically increased the transcription factor signal transducers and activators of transcription 1 (STAT1) DNA binding activity, an effect that was attenuated by PDTC. The role of STAT1 in the regulation of the IL-4-induced MCP-1 gene expression was further confirmed in HUVEC transfected with a reporter construct of the MCP-1 promoter with a mutated STAT1 binding site. These results demonstrate that IL-4-dependent MCP-1 induction in HUVEC is mediated by redox-regulated STAT1 activation.
AB - The present study focused on the molecular signaling pathways of monocyte chemoattractant protein-1 (MCP-1) induction by interleukin-4 (IL-4) in human umbilical vein endothelial cells (HUVEC). RT-PCR showed that MCP-1 mRNA accumulation was markedly increased in IL-4-treated HUVEC in a time- and dose-dependent manner. Antioxidants, such as pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC), significantly inhibited IL-4-induced MCP-1 mRNA expression. These effects correlated well with the PDTC-mediated inhibition of MCP-1 promoter transcriptional activity observed in IL-4-treated HUVEC. IL-4-induced MCP-1 gene expression was paralleled by a concomitant production of MCP-1 protein. In agreement with MCP-1 gene expression, PDTC attenuated IL-4-mediated induction of MCP-1 protein expression. In addition, IL-4 dramatically increased the transcription factor signal transducers and activators of transcription 1 (STAT1) DNA binding activity, an effect that was attenuated by PDTC. The role of STAT1 in the regulation of the IL-4-induced MCP-1 gene expression was further confirmed in HUVEC transfected with a reporter construct of the MCP-1 promoter with a mutated STAT1 binding site. These results demonstrate that IL-4-dependent MCP-1 induction in HUVEC is mediated by redox-regulated STAT1 activation.
KW - Antioxidants
KW - Atherosclerosis
KW - Inflammatory cytokine
KW - Interleukin-4
KW - Monocyte chemoattractant protein-1
KW - Signal transducers and activator of transcription 1
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=0037232666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037232666&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00524.2002
DO - 10.1152/ajpheart.00524.2002
M3 - Article
C2 - 12388243
AN - SCOPUS:0037232666
SN - 0363-6135
VL - 284
SP - H185-H192
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1 53-1
ER -