ICAM-1 and VCAM-1 expression induced by TNF-alpha are inhibited by a glutathione peroxidase mimic.
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are respectively involved in the endothelial recruitment of neutrophils, and in that of lymphocytes or tumor cells, in response to specific signals. We have used the glutathione peroxidase (GPx) mimic BXT-51072 to assess the possibility that endogenous hydroperoxides play a role in the tumor necrosis factor-alpha (TNFalpha)-induced expression of ICAM-1 and VCAM-1 by monolayers of human endothelial cells. The GPx mimic BXT-51072 strongly inhibits the TNFalpha-induced and cycloheximide-sensitive expression of ICAM-1 and VCAM-1. It also inhibits the TNFalpha-induced reorganization of the actin network and the associated formation of stress fibers. Actin reorganization induced by cytochalasin D treatment did not inhibit ICAM-1 expression. Our results are compatible with specific and synergistic effects of endogenous hydroperoxides on the biosynthesis and processing of cell adhesion molecules and cytoskeleton components.
d'Alessio
P
P
INSERM U75, CHU Necker, Laboratoire de Biochimie Pharmacologique et Métabolique, Paris, France. dalessio@necker.fr
Moutet
M
M
Coudrier
E
E
Darquenne
S
S
Chaudiere
J
J
D000199:Actins / Q000096:biosynthesis / Q000187:drug effects; D001393:Azoles / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004336:Drug Antagonism; D004730:Endothelium, Vascular; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D054833:Isoindoles; D018716:Molecular Mimicry; D016566:Organoselenium Compounds / Q000494:pharmacology; D018036:Selenium Compounds / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D000199:Actins; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D018036:Selenium Compounds; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015638:Cytochalasin D; C042986:ebselen; D003513:Cycloheximide; D005979:Glutathione Peroxidase