Document Detail


Binding of pregnancy-specific glycoprotein 17 to CD9 on macrophages induces secretion of IL-10, IL-6, PGE2, and TGF-beta1.
MedLine Citation:
PMID:  15772125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy-specific glycoproteins (PSGs) are a family of secreted proteins produced by the placenta, which are believed to have a critical role in pregnancy success. Treatment of monocytes with three members of the human PSGs induces interleukin (IL)-10, IL-6, and transforming growth factor-beta(1) (TGF-beta(1)) secretion. To determine whether human and murine PSGs have similar functions and use the same receptor, we treated wild-type and CD9-deficient macrophages with murine PSG17N and human PSG1 and -11. Our data show that murine PSG17N induced secretion of IL-10, IL-6, prostaglandin E(2), and TGF-beta(1) and that CD9 expression is required for the observed induction of cytokines. Therefore, the ability of PSG17 to induce anti-inflammatory cytokines parallels that of members of the human PSG family, albeit human and murine PSGs use different receptors, as CD9-deficient and wild-type macrophages responded equally to human PSGs. We then proceeded to examine the signaling mechanisms responsible for the CD9-mediated response to PSG17. Inhibition of cyclooxygenase 2 significantly reduced the PSG17N-mediated increase in IL-10 and IL-6. Further characterization of the response to PSG17 indicated that cyclic adenosine monophosphate-dependent protein kinase A (PKA) is involved in the up-regulation of IL-10 and IL-6, and it is not required for the induction of TGF-beta(1). Conversely, treatment of macrophages with a PKC inhibitor reduced the PSG17-mediated induction of TGF-beta(1), IL-6, and IL-10 significantly. The induction of anti-inflammatory cytokines by various PSGs supports the hypothesis that these glycoproteins have an essential role in the regulation of the maternal immune response in species with hemochorial placentation.
Authors:
Cam T Ha; Roseann Waterhouse; Jennifer Wessells; Julie A Wu; Gabriela S Dveksler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-16
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  77     ISSN:  0741-5400     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-26     Completed Date:  2005-08-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  948-57     Citation Subset:  IM    
Affiliation:
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / metabolism*
Cyclooxygenase 2
Dinoprostone / metabolism
Glycoproteins / metabolism*,  pharmacology
Humans
Inflammation Mediators / metabolism*
Interleukin-10 / metabolism
Interleukin-6 / metabolism
Macrophages / drug effects,  immunology*
Membrane Glycoproteins / metabolism*
Membrane Proteins
Mice
Pregnancy Proteins / metabolism*,  pharmacology
Prostaglandin-Endoperoxide Synthases / metabolism
Protein Kinase C / physiology
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1
Grant Support
ID/Acronym/Agency:
HD35832/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/CD9 antigen; 0/Glycoproteins; 0/Inflammation Mediators; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/Pregnancy Proteins; 0/TGFB1 protein, human; 0/Tgfb1 protein, mouse; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/pregnancy-specific glycoprotein 17, mouse; 130068-27-8/Interleukin-10; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 2.7.11.13/Protein Kinase C

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