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Human Pregnancy-Specific Glycoproteins Function as Immunomodulators In Vitro by Inducing Secretion of IL-10 and IL-6 in Human Monocytes

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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The lack of rejection of the semiallogeneic fetus by the maternal immune system is brought about in part by the maintenance of an anti-inflammatory immune environment at the maternal-fetal interface.The fetoplacental unit produces an array of cytokines and other regulatory molecules that assist in the implantation, survival and development of the fetus. Pregnancy specific glycoproteins pSGs are a family of highly conserved, secreted proteins abundantly produced by the placenta in various species including human, mouse and rat. PSGs are composed of repeated immunoglobulin Ig related domains, and are part of the Ig superfamily. Abnormally low levels of PSGs in maternal serum have been correlated with complications of pregnancy including spontaneous abortion. A peptide derived from the N-terminal domain of human PSG11 has been shown to bind cells of the promonocyte lineage, suggesting a role for PSGs in modulation of macrophage function during pregnancy. We investigated the ability of three recombinant human PSGs pSGI, PSG6 and PSG1I, produced using a baculovirus expression system, to regulate the in vitro production of cytokines by human monocytes. Cytokine secretion by monocytes at 24 hours after treatment was measured by quantitative sandwich ELISA. All three PSGs induced dose-dependent secretion ofIL-l0 and 1L-6. but not secretion of TNF-a, IL-IJ3 or 1L-12. In order to examine the role of the N-terminal Ig-variable-like domain in PSG function, we produced a fusion protein consisting of only the N-terminal domain ofPSG6. The PSG6 N-terminal domain was shown to be sufficient for induction of iIlonocyte secretion of IL-l0 and 1L-6, demonstrating that this domain mediates the interaction with a putative PSG receptor on monocytes.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Genetic Engineering and Molecular Biology

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