Natural and recombinant human glycodelin activate a proapoptotic gene cascade in monocyte cells

摘要: Glycodelin-A (GdA) is a member of the superfamily lipocalins and predominant gly- coprotein secreted by human primate endome- trium in secretory early pregnancy phases. GdA can inhibit NK cell activity, T prolifera- tion, chemotaxis monocytes. Its physiolog- ical function thought to mediate immunotoler- ance at fetomaternal interface. In present studies, we engineered recombinant Gd (rGd) yeast tested its biological effects on monocyte viability. rGd, like natural, purified trial GdA, glycosylated secreted, they both induced apototic changes monocytic U937 cells primary Trypan blue exclusion, nucleosome release, DNA laddering, immunocytochemistry detect free 3-OH ends were used characterize rGd. Using as model, cDNA microarray analyses revealed several pro- an- tiapoptotic genes that up- down-regu- lated, respectively, accordance with kinetics rGd-induced death. Real-time RT-PCR confirmed Bad, Bax, TNF-R1 gene expression increased, whereas Bcl-2A1 proliferation-inducing ligand (APRIL) reduced Transfection assays indicated immunomodulatory actions rGd associated NF-B inhibition. West- ern blotting lysates demonstrated activated caspase-8, -2, -3 execute programmed death these cells. We postulate infiltrating monocytes poten- tially other innate immune decidua might be manipulated this glycoprotein en- hance embryonic implantation rates or conversely, develop novel contraceptive strategies. J. Leu- koc. Biol. 83: 843-852; 2008.