Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-β and prevents dextran sodium sulfate (DSS)-induced colitis in mice.
Transforming growth factor-βs (TGF-βs) are secreted from cells as latent complexes and the activity of TGF-βs is controlled predominantly through activation of these complexes. Tolerance to the fetal allograft is essential for pregnancy success; TGF-β1 and TGF-β2 play important roles in regulating these processes. Pregnancy-specific β-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-β1 and TGF-β2 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 number of T regulatory cells. The PSG1-mediated protection was greatly inhibited by the coadministration of neutralizing anti-TGF-β antibody. Our results indicate that proteins secreted by the placenta directly contribute to the generation of active TGF-β and identify PSG1 as one of the few known biological activators of TGF-β2.
Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Medicine University Berlin, Berlin, Germany.
S M
SM
Blois
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
G
G
Sulkowski
Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Medicine University Berlin, Berlin, Germany.
I
I
Tirado-González
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
J
J
Warren
Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Medicine University Berlin, Berlin, Germany.
N
N
Freitag
Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Medicine University Berlin, Berlin, Germany.
B F
BF
Klapp
Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
D
D
Rifkin
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
I
I
Fuss
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
W
W
Strober
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
G S
GS
Dveksler
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011268:Pregnancy-Specific beta 1-Glycoproteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D016264:Dextran Sulfate