Pregnancy-Specific Glycoproteins Function as Immunomodulators by Inducing Secretion of IL-10, IL-6 and TGF-β1 by Human Monocytes

Authors

  • SARA K. SNYDER,

  • JENNIFER L. WESSELLS,

  • ROSEANN M. WATERHOUSE,

  • GABRIELA S. DVEKSLER,

  • DAVID H. WESSNER,

  • LARRY M. WAHL,

  • WOLFGANG ZIMMERMANN


Address reprint requests to Dr. Gabriela Dveksler, Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda MD 20814.

E-mail: gdveksler@usuhs.mil

Abstract

PROBLEM: Low levels of pregnancy-specific glycoproteins (PSGs) in maternal serum have been correlated with complications of pregnancy. We investigated the ability of human PSGs to regulate in vitro production of cytokines.
METHOD OF STUDY: Human monocytes and murine RAW 264.7 cells were treated with recombinant PSG1, PSG6, PSG11, or a truncated PSG6 consisting of only the N-terminal domain (PSG6N). Cytokine production in response to PSG-treatment was measured by ELISA and/or reverse transcriptase-PCR.
RESULTS: All PSGs tested induced secretion of interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-β1 by both human and murine cells, but not IL-1β, tumor necrosis factor (TNF)-α or IL-12. The N-terminal domain of PSG6 was sufficient for induction of monocyte cytokine secretion. Induction of IL-10 and IL-6 was preceded by an increase in the specific mRNAs.
CONCLUSIONS: PSG1, PSG6, PSG6N, and PSG11 induce dose-dependent secretion of anti-inflammatory cytokines by human monocytes. Human and murine PSGs exhibit cross-species activity. Our results are consistent with a role for PSGs in modulation of the innate immune system.

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