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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Redox-regulated mechanisms of IL-4-induced MCP-1 expression in human vascular endothelial cells.

Authors: Lee, Yong Woo; Hennig, Bernhard; Toborek, Michal

Published In Am J Physiol Heart Circ Physiol, (2003 Jan)

Abstract: 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.

PubMed ID: 12388243 Exiting the NIEHS site

MeSH Terms: Antioxidants/pharmacology; Cells, Cultured; Chemokine CCL2/genetics; Chemokine CCL2/metabolism*; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; DNA/antagonists & inhibitors; DNA/metabolism; Endothelium, Vascular/metabolism*; Gene Expression/drug effects; Humans; Interleukin-4/pharmacology*; Oxidation-Reduction; Proline/analogs & derivatives*; Proline/pharmacology; STAT1 Transcription Factor; Thiocarbamates/pharmacology; Trans-Activators/metabolism; Trans-Activators/physiology; Transcription Factors/physiology

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