Cyclic AMP modulates interleukin-1 action in a cytotoxic T-cell hybridoma.
The induction of cytolytic activity in PC60, a murine T-cell hybridoma, is paralleled by a rise in the level of BLT-esterase (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase), a serine esterase specific for activated T-cells. Both interleukin-1 (IL-1) and dibutyryl cAMP were albe to increase the esterase activity in a dose-dependent and saturable manner. When added in combination the two activators showed a strong synergism: BLT-esterase levels were up to three times higher than the sum of the levels due to dibutyryl cAMP and IL-1 added separately. Stimulators of the adenylate cyclase, such as forskolin and cholera toxin, induced a similar enhancement of the BLT-esterase response to IL-1. PC60 cells did not produce any cAMP in response to IL-1. When the two stimuli were added sequentially a second effect for cAMP emerged: preincubation with dibutyryl cAMP or activators of the adenylate cyclase for 4 h or longer completely blocked the action of subsequently added IL-1. Taken together, the data demonstrate a dual modulatory role for cAMP in T-lymphocytes activated by IL-1.
Schlegel-Haueter
S E
SE
Department of Biochemistry, University of Geneva, Switzerland.
Aebischer
F
F
D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D053804:Granzymes; D006825:Hybridomas; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D015290:Second Messenger Systems; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
D007375:Interleukin-1; D007376:Interleukin-2; D003994:Bucladesine; D000242:Cyclic AMP; D053804:Granzymes; D012697:Serine Endopeptidases