Human Pregnancy-Specific Glycoproteins Functions as Immunomodulators in Vitro by Inducing Secretion of IL-10 and IL-6 in Human Monocytes
Abstract
The lack of rejection of the semiallogeneic fetus by the maternal immune system is brought about in pan by the maintenance of an anti-inflammatory immune environment at the maternal-fetal interface. The fetoplacental unit produces an away 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 pan 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 (PSG1, PSG6 and PSG11), 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 of IL-10 and IL-6, but not secretion of TNF-alpha, IL-1beta or IL-12. In order to examine the role of the N-terminal Ig-variable-like domain in PS6 function, we produced a fusion protein consisting of only the N-terminal domain of PSG6. The PSG6 N- terminal domain was shown to be sufficient for induction of monocyte secretion of IL- 10 and IL-6, demonstrating that this domain mediates the interaction with a putative PSG receptor on monocytes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2000
- Accession Number
- ADA444401
Entities
People
- Sara Snyder
Organizations
- Uniformed Services University of the Health Sciences