Glycodelin-A Stimulates Interleukin-6 Secretion by Human Monocytes and Macrophages through L-selectin and the Extracellular Signal-regulated Kinase Pathway

作者: Cheuk-Lun Lee , Eve Y. F. Lam , Kevin K. W. Lam , Hannu Koistinen , Markku Seppälä

DOI: 10.1074/JBC.M112.385336

关键词:

摘要: Macrophages represent the second major type of decidual leukocytes at fetomaternal interface. Changes in macrophage number and activity are associated with fetal loss pregnancy complications. Glycodelin-A (GdA) is an abundant glycoprotein first-trimester decidua. It involved defense early placental development through its regulatory activities various immune cells. The N-glycosylation GdA mediates binding therefore molecule. In this study, we studied biological functions human monocytes/macrophages. was purified from amniotic fluid by affinity chromatography. treatment did not affect viability, cell death, or phagocytic GdA, but recombinant glycodelin without glycosylation, induced IL-6 production as demonstrated cytokine array, intracellular staining, ELISA. also phosphorylation ERK involvement ERKs induction confirmed using pharmacological inhibitors. Co-immunoprecipitation showed that L-selectin on monocytes/macrophages protein GdA. Treatment anti-L-selectin antibody reduced GdA-induced production. GdA-treated macrophages suppressed IFN-γ expression co-cultured T-helper cells IL-6-dependent manner. These results show interacts to induce activating signaling pathway. turn, increased suppresses cells, which may play important role inducing a Th-2-polarized environment flavors immunotolerance fetoplacental unit.

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