Selective inhibition of E-selectin, ICAM-1, and VCAM in endothelial cells.
Endothelial cells, as they normally exist in the vasculature as quiescent cells, perform several functions. In an inflammatory response, endothelial cells are activated to up-regulate a number of genes, including E-selectin (ELAM-1), VCAM-1, ICAM-1, interleukin (IL)-1, IL-8 and plasminogen activator inhibitor-1 (PAI-1). Very little is known about factors that regulate the activation process. We describe here that a heat-stable protein, normally present in the alpha-globulin fraction of serum, inhibits induced expression of E-selectin, ICAM-1, and VCAM-1 in vitro and also impedes the accumulation of mRNA for these molecules. Inhibition of E-selectin, the only gene tested in this respect, is at the level of transcription. At the same time, the alpha-globulins do not, under the same conditions, repress mRNA accumulation for IL-1, IL-8, or PAI-1. The effect of the inhibitor does not relate to constraints on function of nuclear-factor kappa B, the induced activity of which is not interfered with at the early time points at which the suppression of these three genes is seen.
Stuhlmeier
K M
KM
Sandoz Center for Immunobiology, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Csizmadia
V
V
Cheng
Q
Q
Winkler
H
H
Bach
F H
FH
D000510:Alpha-Globulins / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D019040:E-Selectin; D010450:Endopeptidases / Q000737:chemistry; D004730:Endothelium, Vascular / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D019010:Vascular Cell Adhesion Molecule-1
D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010450:Endopeptidases