Beta-endorphin inhibits interleukin-2 release and expression of interleukin-2 receptors in concanavalin A-stimulated splenic lymphocytes.
beta-endorphin, when added at the same time as the mitogenic lectin concanavalin A to mouse BALB/c spleen lymphocytes, inhibits cell proliferation. The suppressive effect of beta-endorphin is not exercised through a cAMP-dependent mechanism and is also observed when splenic lymphocytes are stimulated with phytohemagglutinin (4 micrograms/ml), anti-CD3 monoclonal antibody, or the Ca2+ ionophore A23187 (250 nM) and phorbol 12-myristate 13-acetate (1 ng/ml). The inhibitory effect of beta-endorphin on lymphocyte proliferation is dose and time dependent: when beta-endorphin is added 20 h after Con A stimulation no suppression of lymphocyte proliferation is observed. beta-Endorphin inhibits, in a dose-dependent manner, the release of interleukin-2 in concanavalin A-stimulated splenic lymphocytes, measured 24 h after stimulation. beta-Endorphin also controls the appearance of interleukin-2 receptors in the plasma membrane, but does not regulate the expression of the c-myc protooncogene. These data indicate that beta-endorphin inhibits lymphocyte activation signal transmission, downstream the generation of the second messengers Ca2+ and diacylglycerol and the expression of the protooncogene c-myc, by blocking interleukin-2 release and interleukin-2 receptors expression. Once the cells are in the G1 stage, beta-endorphin is no longer able to block lymphocyte proliferation.
Garcia
I
I
Instituto Investigaciones Biomédicas, CSIC, Fac. de Medicina, UA, Madrid, Spain.
Perez-Castillo
A
A
Moreno
J
J
Alemany
S
S
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016259:Genes, myc / Q000187:drug effects; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001615:beta-Endorphin / Q000494:pharmacology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D001615:beta-Endorphin