Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-1β Down-regulate Intercellular Adhesion Molecule (ICAM)-2 Expression on the Endothelium

Abstract

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 β2 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-α andIL-1βon ICAM-2 expression on human umbilical vein endothelial cells (HUVECs). Prolonged treatment (24 h) of HUVECs with TNF-α (10 ng/ ml) or IL-1β (34ng/ml) reduced ICAM-2 surface expression to 50% of control, while interferon (IFN)-γ had no effect. The loss in ICAM-2 surface expression correlated with a reduction of ICAM-2 raRNA to ±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-α and IL-lβ 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.

Key Words:

• Endothelium
• Vascular
• cell adhesion molecules
• gene expression
• human
• intercellular junctions