Induction and localization of NOD2 protein in human endothelial cells

Cell Immunol. 2005 Sep;237(1):37-44. doi: 10.1016/j.cellimm.2005.09.006. Epub 2005 Nov 8.

Abstract

NOD2 is mainly expressed in human monocytes/macrophages and intestinal epithelial cells and has been speculated to play in gut physiology. However, whether NOD2 is expressed in vascular endothelium is not currently determined. Human umbilical vascular endothelial cells (HUVECs) minimally expressed NOD2 gene, whereas stimulation of HUVEC with bacterial LPS, IL-1beta, or TNF-alpha resulted in significant up-regulation of NOD2. NOD2 protein was mostly localized in the cytoplasm. Overexpression of wild-type NOD2 (WT-NOD2) gene induced NF-kappaB-dependent transcriptional activity and this activity was further increased by muramyl dipeptide (MDP). Otherwise, down-regulation of WT-NOD2 gene by antisense NOD2 abolished NF-kappaB-dependent transcriptional activity mediated by either WT-NOD2 itself or MDP. Since vascular endothelial cells, like macrophages and epithelial cells, are critical targets for the circulating bacterial molecules such as MDP, collectively, the results presented here suggest that NOD2 may play an important role in recognizing structural patterns of bacterial pathogen in the endothelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / immunology
  • Acetylmuramyl-Alanyl-Isoglutamine / metabolism
  • Adjuvants, Immunologic / metabolism
  • Blotting, Western
  • Cell Line
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism*
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • Intracellular Signaling Peptides and Proteins / drug effects
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Microscopy, Fluorescence
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Nod2 Signaling Adaptor Protein
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Transfection
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adjuvants, Immunologic
  • Interleukin-1
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Acetylmuramyl-Alanyl-Isoglutamine