Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells.
Human atherosclerotic plaques contain numerous smooth muscle cells (SMCs) that express intercellular adhesion molecule-1 (ICAM-1). Expression of ICAM-1 in different cells is known to be regulated by tumor necrosis factor-alpha (TNF-alpha), which has recently been found to be present in the intimal thickening of human arteries. Therefore, we studied the effect of TNF-alpha on ICAM-1 mRNA content and surface expression in cultured human aortic SMCs by using the methods of Northern blotting and immunofluorescence flow cytometry. Under basal conditions of cultivation, ICAM-1 mRNA was not revealed in SMCs. However, treatment of the cells with recombinant human TNF-alpha induced substantial levels of ICAM-1 mRNA. The content of ICAM-1 on the surface of SMCs also increased in a dose- and time-dependent manner after incubation with TNF-alpha. Twenty-four hours of treatment with 10 ng/mL TNF-alpha led to an approximately 10-fold increase in ICAM-1 surface expression in the SMCs. Under the same conditions, pretreatment of SMCs with TNF-alpha resulted in a twofold increase of their adhesiveness for monocytes. In the presence of anti-ICAM-1 monoclonal antibody 10F3, monocyte adhesion to TNF-alpha-pretreated SMCs was significantly inhibited, suggesting that the observed monocyte-SMC interaction involved the ICAM-1 expressed on SMC surfaces as a result of TNF-alpha stimulation. These results led us to propose that TNF-alpha may act a regulator of functional ICAM-1 expression on the SMC surface and thus can increase the possibility of interactions between mononuclear cells and SMCs in atherosclerotic plaques.
Couffinhal
T
T
Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 8 de Cardiologie, Pessac, France.
Duplàa
C
C
Labat
L
L
Lamaziere
J M
JM
Moreau
C
C
Printseva
O
O
Bonnet
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015335:Molecular Probes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1