Pregnancy-specific glycoproteins function as immunomodulators by inducing secretion of IL-10, IL-6 and TGF-β1 by human monocytes

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. Methods 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 of PSGs in modulation of the innate immune system.