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

Yong Woo Lee, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)H185-H192
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number1 53-1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Antioxidants
  • Atherosclerosis
  • Inflammatory cytokine
  • Interleukin-4
  • Monocyte chemoattractant protein-1
  • Signal transducers and activator of transcription 1
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology

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