Interleukin-1 modulates protein tyrosine phosphatase activity and permeability of brain endothelial cells.
Interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6), both known to be able to open the blood-brain barrier (BBB), downregulated plasma membrane-associated tyrosine phosphatase activity in primary porcine brain endothelial cells (PBEC). In contrast, transforming growth factor beta (TGF-beta) upregulated PTP activity and tumor necrosis factor alpha (TNF-alpha) had no effect. Plasma membrane-associated PTP activity of PBEC was upregulated at contact inhibited growth arrest. Tightly confluent cells reduced 3H-inulin permeability by 34% compared with just confluent cells indicating the formation of barrier properties. The decrease in permeability temporally correlated with the elevated PTP activity of the cells at growth arrest and was reversed to control by IL-1 alpha. Vanadate, a broad-specificity PTP inhibitor, also enhanced 3H-inulin permeability. These data suggest that IL-1 alpha-induced endothelial permeability could be controlled through lowering PTP activity.
Gloor
S M
SM
Swiss Federal Institute of Technology, ETH Zentrum, Zürich, Switzerland.
Weber
A
A
Adachi
N
N
Frei
K
K
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D016207:Cytokines; D007375:Interleukin-1; D017027:Protein Tyrosine Phosphatases