Recombinant human interleukin-1 inhibits the induction by dexamethasone of alkaline phosphatase activity in murine capillary endothelial cells.
A mutual antagonism exists between interleukin-1s (IL-1s) as pro-inflammatory and glucocorticoids as anti-inflammatory mediators. This report examines the effects of IL-1 on the induction by dexamethasone of alkaline phosphatase in LEII murine endothelial cells. Dexamethasone increases the specific activity of alkaline phosphatase in a time- and dose-dependent fashion (maximum 14-fold induction at 10(-6) M, IC50 = 10(-8) M), and this induction can be completely inhibited by simultaneous incubation with picomolar concentrations of recombinant human IL-1 alpha or IL-1 beta. This IL-1-mediated antagonism of dexamethasone activity is not due to a down-regulation of glucocorticoid receptors in the cell line used, because the number of receptors and their affinity for dexamethasone is unchanged in IL-1-treated cells. However, induction of alkaline phosphatase by dexamethasone in LEII cells is receptor-mediated, since it can also be inhibited by glucocorticoid-receptor antagonists.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002196:Capillaries; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011994:Recombinant Proteins
D005938:Glucocorticoids; D007375:Interleukin-1; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D003907:Dexamethasone; D000469:Alkaline Phosphatase