Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium

Cell Adhes Commun. 1998;6(5):381-400. doi: 10.3109/15419069809109147.


Leukocyte recruitment is a crucial step in inflammation. Inflammatory stimuli upregulate the expression of some endothelial adhesion molecules, such as E-selectin or ICAM-1, but not of others such as ICAM-2. ICAM-2, a constitutively expressed endothelial ligand for beta2 integrins LFA-1 and Mac-1, is involved in leukocyte adhesion to resting endothelium and in transmigration in vitro, however its role in inflammation is unclear. We have studied the effect of TNF-alpha and IL-1beta on ICAM-2 expression on human umbilical vein endothelial cells (HUVECs). Prolonged treatment (24 h) of HUVECs with TNF-alpha (10 ng/ml) or IL-1beta (34 ng/ml) reduced ICAM-2 surface expression to 50% of control, while interferon (IFN)-gamma had no effect. The loss in ICAM-2 surface expression correlated with a reduction of ICAM-2 mRNA to approximately 40% of control after 24 h of cytokine treatment. The activity of an ICAM-2 promoter reporter plasmid transfected into HUVECs was down-regulated by TNF-alpha and IL-1beta to similar values. Thus inflammatory cytokines inhibit ICAM-2 transcription, despite the absence of known cytokine-responsive elements in the promoter. Immunocytochemistry on HUVEC monolayers showed that ICAM-2 expression, mainly at the cell junctions in resting cells, was markedly decreased by cytokine treatment. This data suggest that ICAM-2 expression on the endothelium may be regulated during inflammation.

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, CD / metabolism*
  • Base Sequence
  • Blotting, Northern
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation*
  • Endothelium, Vascular / metabolism*
  • Flow Cytometry
  • Genes, Reporter
  • Humans
  • Inflammation
  • Interleukin-1 / metabolism*
  • Luciferases / metabolism
  • Lymphotoxin-alpha / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*
  • Umbilical Cord / metabolism


  • Antibodies, Monoclonal
  • Antigens, CD
  • Cell Adhesion Molecules
  • ICAM2 protein, human
  • Interleukin-1
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Luciferases