Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-β and prevents dextran sodium sulfate (DSS)-induced colitis in mice

Transforming growth factor-beta s (TGF-beta s) are secreted from cells as latent complexes and the activity of TGF-beta s is controlled predominantly through activation of these complexes. Tolerance to the fetal allograft is essential for pregnancy success; TGF-beta 1 and TGF-beta 2 play important roles in regulating these processes. Pregnancy-specific beta-glycoproteins (PSGs) are present in the maternal circulation at a high concentration throughout pregnancy and have been proposed to have anti-inflammatory functions. We found that recombinant and native PSG1 activate TGF-beta 1 and TGF-beta 2 in vitro. Consistent with these findings, administration of PSG1 protected mice from dextran sodium sulfate (DSS)-induced colitis, reduced the secretion of pro-inflammatory cytokines, and increased the numberof Tregulatory cells. The PSG1-mediated protectionwasgreatly inhibited by the coadministration of neutralizing anti-TGF-beta antibody. Our results indicate that proteins secreted by the placenta directly contribute to the generation of active TGF-beta and identify PSG1 as one of the few known biological activators of TGF-beta 2.