Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture

We have previously shown that somatostatin (SRIF) is synthesized in B and T lymphocytes of rat spleen and thymus and released into the medium of cultured lymphocytes. To determine the role of SRIF in the control of lymphocytes proliferation, the expression of SRIF in normal lymphocytes was inhibited using a 3'-terminal phosphorothioate-modified antisense oligonucleotide complementary to a sequence that includes the translation start site of the rat SRIF messenger RNA. Spleens were obtained from adult male rats, and their lymphocytes were cultured for 24 or 72 h to measure SRIF content and cell proliferation, respectively. For the proliferation studies, [3H]thymidine was incorporated during the final 18 h. The lymphocytes were incubated with 15-30 micrograms/ml SRIF antisense and control antisense. SRIF antisense (25 micrograms/ml) increased lymphocyte proliferation 15-fold (P < or = 0.001), reaching a plateau (25- to 30-fold increase) between 25-30 micrograms/ml SRIF antisense. SRIF was extracted from lym...