Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults.
Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.
Stanimirovic
D B
DB
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada.
Wong
J
J
Shapiro
A
A
Durkin
J P
JP
D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008954:Models, Biological; D014158:Transcription, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D016207:Cytokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1