Pregnancy-specific glycoproteins function as immunomodulators by inducing secretion of IL-10, IL-6 and TGF-beta1 by human monocytes.
OBJECTIVE
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
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)-beta1 by both human and murine cells, but not IL-1beta, tumor necrosis factor (TNF)-alpha 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.
Snyder
S K
SK
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Wessner
D H
DH
Wessells
J L
JL
Waterhouse
R M
RM
Wahl
L M
LM
Zimmermann
W
W
Dveksler
G S
GS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000187:drug effects*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology*; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000235:genetics / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000276:Adjuvants, Immunologic; D006023:Glycoproteins; D015850:Interleukin-6; D007378:Interleukins; C075077:PSG6 protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D011268:Pregnancy-Specific beta 1-Glycoproteins; D011993:Recombinant Fusion Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10