{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:59:33Z","timestamp":1761217173422,"version":"3.37.3"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2008,1,18]],"date-time":"2008-01-18T00:00:00Z","timestamp":1200614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HD44008"],"award-info":[{"award-number":["R01-HD44008"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2032-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 indicated that the immunomodulatory actions of rGd were associated with NF-\u03baB inhibition. Western blotting of U937 and primary monocyte lysates demonstrated that rGd activated caspase-8, -2, and -3 to execute programmed cell death in these cells. We postulate that infiltrating monocytes and potentially other innate immune cells of the decidua might be manipulated by this glycoprotein to enhance embryonic implantation rates or conversely, to develop novel contraceptive strategies.<\/jats:p>","DOI":"10.1189\/jlb.0406291","type":"journal-article","created":{"date-parts":[[2008,1,19]],"date-time":"2008-01-19T02:09:57Z","timestamp":1200708597000},"page":"843-852","source":"Crossref","is-referenced-by-count":22,"title":["Natural and recombinant human glycodelin activate a proapoptotic gene cascade in monocyte cells"],"prefix":"10.1093","volume":"83","author":[{"given":"Meng Kian","family":"Tee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California , San Francisco, California , USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Louis","family":"Vigne","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California , San Francisco, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Emory University School of Medicine , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert N","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California , San Francisco, California , USA"},{"name":"Department of Gynecology and Obstetrics, Emory University School of Medicine , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,1,18]]},"reference":[{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1210\/er.2001-0026","article-title":"Glycodelin: a major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation","volume":"23","author":"Seppala","year":"2002","journal-title":"Endocr. Rev."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"25580","DOI":"10.1074\/jbc.M504103200","article-title":"Glycodelin-S in human seminal plasma reduces cholesterol efflux and inhibits capacitation of spermatozoa","volume":"280","author":"Chiu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1043-2760(00)00365-9","article-title":"Glycodelins","volume":"12","author":"Seppala","year":"2001","journal-title":"Trends Endocrinol. Metab."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/molehr\/gag008","article-title":"The induction of baboon glycodelin expression by progesterone is not through Sp1","volume":"9","author":"Jaffe","year":"2003","journal-title":"Mol. Hum. Reprod."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1210\/endo.143.6.8885","article-title":"Global gene profiling in human endometrium during the window of implantation","volume":"143","author":"Kao","year":"2002","journal-title":"Endocrinology"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/molehr\/gag004","article-title":"Determination of the transcript profile of human endometrium","volume":"9","author":"Borthwick","year":"2003","journal-title":"Mol. Hum. Reprod."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0303-7207(95)03674-V","article-title":"Differential gene regulation by estrogen and progesterone in the primate endometrium","volume":"115","author":"Ace","year":"1995","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/molehr\/5.4.372","article-title":"Relaxin stimulates glycodelin mRNA and protein concentrations in human endometrial glandular epithelial cells","volume":"5","author":"Tseng","year":"1999","journal-title":"Mol. Hum. Reprod."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1073\/pnas.96.5.2543","article-title":"Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity","volume":"96","author":"Fazleabas","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0002-9378(00)70333-4","article-title":"Effects of progestins and relaxin on glycodelin gene expression in human endometrial cells","volume":"182","author":"Taylor","year":"2000","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0303-7207(01)00450-6","article-title":"Ligand activated hPR modulates the glycodelin promoter activity through the Sp1 sites in human endometrial adenocarcinoma cells","volume":"176","author":"Gao","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1677\/JME-06-0030","article-title":"Histone deacetylase inhibition and progesterone act synergistically to stimulate baboon glycodelin gene expression","volume":"38","author":"Jaffe","year":"2007","journal-title":"J. Mol. Endocrinol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1600-0897.1991.tb00713.x","article-title":"Suppression by human placental protein 14 of natural killer cell activity","volume":"26","author":"Okamoto","year":"1991","journal-title":"Am. J. Reprod. Immunol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"17101","DOI":"10.1074\/jbc.M010451200","article-title":"Purification and characterization of an immunomodulatory endometrial protein, glycodelin","volume":"276","author":"Vigne","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2023033005450468500_","first-page":"271","article-title":"Mechanism of the immunomodulatory activity of glycodelin","volume":"49","author":"Karande","year":"2005","journal-title":"Indian J. Physiol. Pharmacol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1095\/biolreprod.103.017574","article-title":"Dendritic cells in the human decidua","volume":"69","author":"Gardner","year":"2003","journal-title":"Biol. Reprod."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0014-5793(98)01184-3","article-title":"A receptor for the lipocalin placental protein 14 on human monocytes","volume":"436","author":"Miller","year":"1998","journal-title":"FEBS Lett."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0008-8749(03)00129-1","article-title":"Placental protein 14 regulates selective B cell responses","volume":"222","author":"Yaniv","year":"2003","journal-title":"Cell. Immunol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0015-0282(02)03325-3","article-title":"Emerging role of genomics in endometriosis research","volume":"78","author":"Taylor","year":"2002","journal-title":"Fertil. Steril."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1210\/en.2006-1692","article-title":"Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis","volume":"148","author":"Burney","year":"2007","journal-title":"Endocrinology"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1600-0897.1990.tb00672.x","article-title":"Evasive strategies of trophoblast cells: selective expression of membrane antigens","volume":"23","author":"Hunt","year":"1990","journal-title":"Am. J. Reprod. Immunol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jsgi.2005.02.004","article-title":"Effects of phorbol dibutyrate on cell proliferation, apoptosis, and tumor necrosis factor-\u03b1 expression in human endometrial adenocarcinoma cells","volume":"12","author":"Wieser","year":"2005","journal-title":"J. Soc. Gynecol. Investig."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000068952","article-title":"Thiazolidinedione inhibition of peritoneal inflammation","volume":"55","author":"Hornung","year":"2003","journal-title":"Gynecol. Obstet. Invest."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0168-1656(00)00268-6","article-title":"Expression of a mammalian \u03b1 2,6-sialyltransferase gene in Pichia pastoris","volume":"81","author":"Chotigeat","year":"2000","journal-title":"J. Biotechnol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1074\/jbc.M306673200","article-title":"Glycodelin A, not glycodelin S, is apoptotically active. Relevance of sialic acid modification","volume":"279","author":"Mukhopadhyay","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1016\/j.febslet.2007.07.078","article-title":"Differential sialylation regulates the apoptotic activity of glycodelin A","volume":"581","author":"Poornima","year":"2007","journal-title":"FEBS Lett."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1074\/jbc.M310480200","article-title":"Analysis of the role of oligosaccharides in the apoptotic activity of glycodelin A","volume":"279","author":"Jayachandran","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1016\/S0021-9258(19)42503-9","article-title":"On the mechanism of erythropoietin-induced differentiation. 13. The role of sialic acid in erythropoietin action","volume":"249","author":"Goldwasser","year":"1974","journal-title":"J. Biol. Chem."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1021\/bi00469a021","article-title":"Glycosylation at Asn-184 inhibits the conversion of single-chain to two-chain tissue-type plasminogen activator by plasmin","volume":"29","author":"Wittwer","year":"1990","journal-title":"Biochemistry"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0014-5793(99)00490-1","article-title":"Glycodelin and \u03b2-lactoglobulin, lipocalins with a high structural similarity, differ in ligand binding properties","volume":"450","author":"Koistinen","year":"1999","journal-title":"FEBS Lett."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.2001.tb03785.x","article-title":"Embryo effects in human implantation: embryonic regulation of endometrial molecules in human implantation","volume":"943","author":"Simon","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023033005450468500_","first-page":"4853","article-title":"Macrophage infiltration and angiogenesis in endometrial cancer","volume":"20","author":"Hashimoto","year":"2000","journal-title":"Anticancer Res."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1749-6632.2002.tb02769.x","article-title":"Angiogenic factors in endometriosis","volume":"955","author":"Taylor","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/GCO.0b013e328133885f","article-title":"Role of chemokines in the endometrium and in embryo implantation","volume":"19","author":"Hannan","year":"2007","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/0092-8674(93)90464-2","article-title":"A novel domain within the 55 kd TNF receptor signals cell death","volume":"74","author":"Tartaglia","year":"1993","journal-title":"Cell"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbamcr.2003.10.011","article-title":"Role of Bcl-2 family members in immunity and disease","volume":"1644","author":"Droin","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1023\/A:1016167228059","article-title":"Initiator caspases in apoptosis signaling pathways","volume":"7","author":"Chen","year":"2002","journal-title":"Apoptosis"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"9490","DOI":"10.1158\/0008-5472.CAN-07-0598","article-title":"The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation","volume":"67","author":"Rosato","year":"2007","journal-title":"Cancer Res."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S146239940200546X","article-title":"Sphingolipid signaling: molecular basis and role in TNF-\u03b1-induced cell death","volume":"4","author":"Malagarie-Cazenave","year":"2002","journal-title":"Expert Rev. Mol. Med."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00277-005-1065-x","article-title":"Apoptosis: mechanisms and relevance in cancer","volume":"84","author":"Vermeulen","year":"2005","journal-title":"Ann. Hematol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1101\/gad.13.15.1899","article-title":"BCL-2 family members and the mitochondria in apoptosis","volume":"13","author":"Gross","year":"1999","journal-title":"Genes Dev."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.ajog.2005.05.073","article-title":"Glycodelin reduces carcinoma-associated gene expression in endometrial adenocarcinoma cells","volume":"193","author":"Koistinen","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1084\/jem.188.6.1185","article-title":"APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth","volume":"188","author":"Hahne","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1359-6101(03)00023-6","article-title":"The TNF family members BAFF and APRIL: the growing complexity","volume":"14","author":"Mackay","year":"2003","journal-title":"Cytokine Growth Factor Rev."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1182\/blood-2003-02-0540","article-title":"Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway","volume":"103","author":"Kern","year":"2004","journal-title":"Blood"},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.4049\/jimmunol.172.5.3268","article-title":"Lymphoma B cells evade apoptosis through the TNF family members BAFF\/BLyS and APRIL","volume":"172","author":"He","year":"2004","journal-title":"J. Immunol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1101\/gad.13.4.382","article-title":"The prosurvival Bcl-2 homolog Bfl-1\/A1 is a direct transcriptional target of NF-\u03baB that blocks TNF\u03b1-induced apoptosis","volume":"13","author":"Zong","year":"1999","journal-title":"Genes Dev."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"8855","DOI":"10.1128\/MCB.20.23.8855-8865.2000","article-title":"Macrophages require constitutive NF-B activation to maintain A1 expression and mitochondrial homeostasis","volume":"20","author":"Pagliari","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2023033005450468500_","doi-asserted-by":"crossref","first-page":"18099","DOI":"10.1074\/jbc.M908925199","article-title":"A1 functions at the mitochondria to delay endothelial apoptosis in response to tumor necrosis factor","volume":"275","author":"Duriez","year":"2000","journal-title":"J. Biol. Chem."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/4\/843\/49635214\/jlb0843.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/83\/4\/843\/49635214\/jlb0843.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T22:34:03Z","timestamp":1684190043000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/83\/4\/843\/6975702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,18]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2008,1,18]]},"published-print":{"date-parts":[[2008,4,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0406291","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"type":"print","value":"0741-5400"},{"type":"electronic","value":"1938-3673"}],"subject":[],"published-other":{"date-parts":[[2008,4]]},"published":{"date-parts":[[2008,1,18]]}}}