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Article: Glycodelin-A stimulates interleukin-6 secretion by human monocytes and macrophages through L-selectin and the extracellular signal-regulated kinase pathway

TitleGlycodelin-A stimulates interleukin-6 secretion by human monocytes and macrophages through L-selectin and the extracellular signal-regulated kinase pathway
Authors
KeywordsCytokine
ERK
Glycoprotein
Macrophages
Monocytes
Pregnancy
Sialic Acid
T-cell
L-selectin
Glycodelin-A
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2012, v. 287 n. 44, p. 36999-37009 How to Cite?
AbstractMacrophages represent the second major type of decidual leukocytes at the fetomaternal interface. Changes in macrophage number and activity are associated with fetal loss and pregnancy complications. Glycodelin-A (GdA) is an abundant glycoprotein in the first-trimester decidua. It is involved in fetomaternal defense and early placental development through its regulatory activities in various immune cells. The N-glycosylation of GdA mediates the binding and therefore the activities of the molecule. In this study, we studied the biological activities of GdA in the functions of human monocytes/macrophages. GdA was purified from amniotic fluid by affinity chromatography. GdA treatment did not affect the viability, cell death, or phagocytic activity of the monocytes/macrophages. GdA, but not recombinant glycodelin without glycosylation, induced IL-6 production as demonstrated by cytokine array, intracellular staining, and ELISA. GdA also induced phosphorylation of ERK in monocytes/macrophages. The involvement of ERKs in IL-6 induction was confirmed using pharmacological inhibitors. Co-immunoprecipitation showed that L-selectin on the monocytes/macrophages was the binding protein of GdA. Treatment with anti-L-selectin antibody reduced GdA binding and GdA-induced IL-6 production. GdA-treated macrophages suppressed IFN-γ expression by co-cultured T-helper cells in an IL-6-dependent manner. These results show that GdA interacts with L-selectin to induce IL-6 production in monocytes/macrophages by activating the ERK signaling pathway. In turn, the increased IL-6 production suppresses IFN-γ expression in T-helper cells, which may play an important role in inducing a Th-2-polarized cytokine environment that flavors the immunotolerance of the fetoplacental unit.
Persistent Identifierhttp://hdl.handle.net/10722/186399
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, CL-
dc.contributor.authorLam, EYF-
dc.contributor.authorLam, KKW-
dc.contributor.authorKoistinen, H-
dc.contributor.authorSeppälä, M-
dc.contributor.authorNg, EHY-
dc.contributor.authorYeung, WSB-
dc.contributor.authorChiu, PCN-
dc.date.accessioned2013-08-20T12:07:44Z-
dc.date.available2013-08-20T12:07:44Z-
dc.date.issued2012-
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287 n. 44, p. 36999-37009-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/186399-
dc.description.abstractMacrophages represent the second major type of decidual leukocytes at the fetomaternal interface. Changes in macrophage number and activity are associated with fetal loss and pregnancy complications. Glycodelin-A (GdA) is an abundant glycoprotein in the first-trimester decidua. It is involved in fetomaternal defense and early placental development through its regulatory activities in various immune cells. The N-glycosylation of GdA mediates the binding and therefore the activities of the molecule. In this study, we studied the biological activities of GdA in the functions of human monocytes/macrophages. GdA was purified from amniotic fluid by affinity chromatography. GdA treatment did not affect the viability, cell death, or phagocytic activity of the monocytes/macrophages. GdA, but not recombinant glycodelin without glycosylation, induced IL-6 production as demonstrated by cytokine array, intracellular staining, and ELISA. GdA also induced phosphorylation of ERK in monocytes/macrophages. The involvement of ERKs in IL-6 induction was confirmed using pharmacological inhibitors. Co-immunoprecipitation showed that L-selectin on the monocytes/macrophages was the binding protein of GdA. Treatment with anti-L-selectin antibody reduced GdA binding and GdA-induced IL-6 production. GdA-treated macrophages suppressed IFN-γ expression by co-cultured T-helper cells in an IL-6-dependent manner. These results show that GdA interacts with L-selectin to induce IL-6 production in monocytes/macrophages by activating the ERK signaling pathway. In turn, the increased IL-6 production suppresses IFN-γ expression in T-helper cells, which may play an important role in inducing a Th-2-polarized cytokine environment that flavors the immunotolerance of the fetoplacental unit.-
dc.languageeng-
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistry-
dc.subjectCytokine-
dc.subjectERK-
dc.subjectGlycoprotein-
dc.subjectMacrophages-
dc.subjectMonocytes-
dc.subjectPregnancy-
dc.subjectSialic Acid-
dc.subjectT-cell-
dc.subjectL-selectin-
dc.subjectGlycodelin-A-
dc.titleGlycodelin-A stimulates interleukin-6 secretion by human monocytes and macrophages through L-selectin and the extracellular signal-regulated kinase pathway-
dc.typeArticle-
dc.identifier.emailLee, CL: kcllee@hku.hk-
dc.identifier.emailNg, EHY: nghye@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hk-
dc.identifier.emailChiu, PCN: pchiucn@hku.hk-
dc.identifier.authorityLee, CL=rp02515-
dc.identifier.authorityNg, EHY=rp00426-
dc.identifier.authorityYeung, WSB=rp00331-
dc.identifier.authorityChiu, PCN=rp00424-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M112.385336-
dc.identifier.pmid22977256-
dc.identifier.pmcidPMC3481301-
dc.identifier.scopuseid_2-s2.0-84868224949-
dc.identifier.hkuros218453-
dc.identifier.volume287-
dc.identifier.issue44-
dc.identifier.spage36999-
dc.identifier.epage37009-
dc.identifier.isiWOS:000310588500035-
dc.publisher.placeUnited States-
dc.identifier.issnl0021-9258-

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