Suppression of zinc finger protein 580 by high oxLDL/LDL-ratios is followed by enhanced expression of endothelial IL-8

Atherosclerosis. 2011 May;216(1):103-8. doi: 10.1016/j.atherosclerosis.2011.01.017. Epub 2011 Jan 22.

Abstract

Objective: The Interleukin 8 (IL-8) response of endothelial cells to lipoproteins has well known implications for the development and progression of atherosclerosis. In this study we sought for the role of zinc finger protein 580 (ZNF580) in the endothelial IL-8 response to lipoproteins.

Methods: In human umbilical vein endothelial cells (HUVEC) ZNF580 and IL-8 levels were examined by real-time-RT-PCR, immunoblotting and immunostaining or ELISA, respectively.

Results: ZNF580 is located in the nucleus and regulated by LDL and HDL depending on the oxLDL/LDL-ratio but not by TNFα. IL-8 expression profiles are inversely influenced by the oxLDL/LDL-ratio, both in vitro and in vivo. Knock down of ZNF580 enhances the expression and release of IL-8 and increases monocyte arrest under flow conditions in vitro.

Conclusions: ZNF580 is a novel factor in the lipoprotein-dependent regulation of IL-8 and monocyte arrest. Therefore it may be a new potential target for intervention in atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control
  • Blotting, Western
  • Cell Adhesion
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism*
  • Monocytes / metabolism
  • Polymerase Chain Reaction
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • ZNF580 protein, human
  • oxidized low density lipoprotein