Glucocorticoids modulate the induction of BLTE/granzyme A activity in the murine T cell hybridoma PC60.
The cytolytic granule-associated serine esterase granzyme A cleaves the synthetic substrate benzyloxycarbonyl-L-lysinate-thiobenzylester (BLT) and has been described as a marker for cytotoxic T lymphocyte (CTL) activation. We recently showed that BLT-esterase activity (BLTE activity) can be induced in the murine CTL-hybridoma PC60 by exogenous interleukin-1 (IL-1) and/or a rise of the intracellular cAMP level, although cAMP does not act as a second messenger for IL-1 in this system. The present study demonstrates that glucocorticoids (GC) such as dexamethasone and hydrocortisone efficiently inhibit the induction of BLTE activity by IL-1 and/or cAMP and downregulate the basal BLTE levels in PC60 cells; these results could be reproduced in part with progesterone and were steroid class-specific, since estrogen did not affect the induction of BLTE activity. The GC-induced effects on the production of BLTE activity required the activation of specific GC receptors, since induction of the activity could be restored upon addition of the contragestative drug RU 38486; they further could not be related to any alteration of the cellular metabolism of arachidonic acid and did not appear to be mediated by secreted macromolecules such as lipocortins.
Aebischer
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Department of Biochemistry, University of Geneva, Switzerland.
Schlegel-Haueter
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D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D053804:Granzymes; D006825:Hybridomas; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology
D017302:Annexins; D002135:Calcium-Binding Proteins; D007375:Interleukin-1; D015735:Mifepristone; D011374:Progesterone; D003907:Dexamethasone; D000242:Cyclic AMP; D053804:Granzymes; D012697:Serine Endopeptidases; D006854:Hydrocortisone