Glucocorticoid inhibition of urokinase-like plasminogen activators in cultured human lymphoblasts.
Two human lymphoblast cell lines, LICR-LON-HMy2 (HMy2 cells) and GM4672A cells, are moderately growth inhibited by dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl-11 beta, 17 alpha, 21-triol-3,20-dione) (Dex). Both cell types secrete a urokinase (UK)-like plasminogen activator (PA). Treatment of both HMy2 and GM4672A cells with Dex for 1-4 days inhibits extracellular PA activity in a concentration-dependent manner, being half-maximal at approximately 1 X 10(-9)M. Inhibition of PA in both cell types is specific for active glucocorticoids, and this specificity parallels the ability of various steroids to bind to glucocorticoid receptors. HMy2 cell PA is fully suppressible by Dex, whereas up to one third of the activator expressed by GM4672A cells is resistant to glucocorticoid inhibition. Mixing experiments using a UK standard and conditioned media from Dex-treated cells suggest an absence of glucocorticoid-inducible inhibitors to UK or plasmin in both cell types. However, conditioned media from Dex-treated GM4672A cells inhibits a portion of the homologous cellular activator in conditioned media from control GM4672A cells. Thus, low levels of glucocorticoid-inducible inhibitors may contribute to, but cannot fully account for, Dex inhibition of GM4672A PA activity. Glucocorticoid-inducible inhibitors in HMy2 cells are either totally absent or are present at undetectable levels. Thus, regulation of UK-like PAs in HMy2 and GM4672A cells differs with respect to the extent to which glucocorticoids inhibit constitutively expressed activator levels, as well as the possible contribution of glucocorticoid-inducible inhibitors to the regulatory process in GM4672A cells.
D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013379:Substrate Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D015849:Plasminogen Inactivators; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator