Biological activity of analogs of the peptide hormone luliberin in the regulation of the immune response of T cells

Abstract

The ability of the antitumor analogs of luliberin (LH-RH), a hypothalamic peptide hormone, to stimulate the immune function of T cells is examined in experiments with the gene coding for interleukin-2 (IL-2). Recombinant MIL2C or 4×Pu DNA containing the marker gene of chloramphenicol acetyltransferase (CAT) under the control of a 2.2 kb promoter of murine IL-2 gene or four copies of purine-rich element (from −292 to −246 base pairs), respectively, is injected inXenopus laevis oocytes. The promoter activity is blocked by inoculation of the protein fraction of nuclear extracts from resting mouse splenic T cells. The IL-2 gene promoter is dereppressed after injection of the short LH-RH analog L1 (7 amino acid residues) into the oocyte nucleus or cytoplasm. The addition of L1 or L2 (an LH-RH analog consisting of 10 amino acid residues) to the incubation medium activates mouse splenic T cells and stimulates the synthesis of IL-2 mRNA 2- to 3-fold more intensely than ConA+rIL-2, judging from dot-blot andin situ hybridization data. Cytological analysis of cell culture shows that the presence of L1 and L2 peptides in the culture medium promotes differentiation of T cells. It is hypothesized that the antitumor activity of these peptides is associated with the stimulation of IL-2 synthesis.