Dexamethasone inhibits antitumor potential of activated macrophages by a receptor mediated action.
The capacity to inhibit P815 mastocytoma growth was induced in macrophages elicited by trehalose dimycolate by a short in vitro treatment with 10 ng/ml LPS. Activation by LPS was associated with a 3 fold increase in the rate of glucose consumption by macrophages. Incubation of activated macrophages with the glucocorticoid dexamethasone (greater than or equal to 10(-8) M) for several hours (greater than or equal to 5 h) resulted in an inhibition of antitumoral activity and a decrease of glucose consumption. Hydrogen peroxide production is a property expressed by trehalose dimycolate-elicited macrophages independently of the presence of LPS. The capacity to release hydrogen peroxide upon triggering was not affected by a pretreatment of macrophages by dexamethasone. The antiglucocorticoid compound RU 38486, known to bind with a high affinity to glucocorticoid receptors without agonist effect, prevented the inhibitory actions of dexamethasone, indicating that these are receptor-mediated.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004963:Estrenes / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015735:Mifepristone; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D004963:Estrenes; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D015735:Mifepristone; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D005947:Glucose