Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium.
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.
McLaughlin
F
F
Vascular Disease Unit, GlaxoWellcome Medicines Research Centre, Herts, UK.
Hayes
B P
BP
Horgan
C M
CM
Beesley
J E
JE
Campbell
C J
CJ
Randi
A M
AM
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014470:Umbilical Cord / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases