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

Leukocyte recruitment is a crucial step in inflammation. Inflammatory stimu li upregulate the expression of some endothelial adhesion molecules, such a s E-selectin or ICAM-1, but not of others such as ICAM-2. ICAM-2, a constit utively expressed endothelial ligand for beta 2 integrins LFA-1 and Mac-1, is involved in leukocyte adhesion to resting endothelium and in transmigrat ion in vitro, however its role in inflammation is unclear. We have studied the effect of TNF-alpha and IL-1 beta on ICAM-2 expression on human umbilic al vein endothelial cells (HUVECs). Prolonged treatment (24 h) of HUVECs wi th TNF-alpha (10 ng/ml) or IL-1 beta (34 ng/ml) reduced ICAM-2 surface expr ession to 50% of control, while interferon (IFN)-gamma had no effect. The l oss in ICAM-2 surface expression correlated with a reduction of ICAM-2 mRNA to approximate to 40% of control after 24 h of cytokine treatment. The act ivity of an ICAM-2 promoter reporter plasmid transfected into HUVECs was do wnregulated by TNF-alpha and IL-1 beta to similar values. Thus inflammatory cytokines inhibit ICAM-2 transcription, despite the absence of known cytok ine-responsive elements in the promoter. Immunocytochemistry on HUVEC monol ayers showed that ICAM-2 expression, mainly at the cell junctions in restin g cells, was markedly decreased by cytokine treatment. This data suggest th at ICAM-2 expression on the endothelium may be regulated during inflammatio n.