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

Journal of Leukocyte Biology
Meng Kian TeeRobert N Taylor

Abstract

Glycodelin-A (GdA) is a member of the superfamily of lipocalins and the predominant glycoprotein secreted by human and primate endometrium in the secretory and early pregnancy phases. GdA can inhibit NK cell activity, T cell proliferation, and chemotaxis of monocytes. Its physiological function is thought to mediate immunotolerance at the fetomaternal interface. In the present studies, we engineered recombinant Gd (rGd) in yeast and tested its biological effects on monocyte viability. rGd, like the natural, purified endometrial GdA, is glycosylated and secreted, and they both induced apototic changes in monocytic U937 cells and primary human monocytes. Trypan blue exclusion, nucleosome release, DNA laddering, and immunocytochemistry to detect free 3'-OH DNA ends were used to characterize the effects of GdA and rGd. Using U937 cells as a model, cDNA microarray analyses revealed several pro- and antiapoptotic genes that were up- and down-regulated, respectively, in accordance with the kinetics of rGd-induced monocyte cell death. Real-time RT-PCR confirmed that Bad, Bax, and TNF-R1 gene expression were increased, whereas Bcl-2A1 and a proliferation-inducing ligand (APRIL) were reduced by rGd. Transfection assays in U937 cells indi...Continue Reading

Citations

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