Document Detail

The granzyme B inhibitor, PI-9, is differentially expressed during placental development and up-regulated in hydatidiform moles.
MedLine Citation:
PMID:  16310039     Owner:  NLM     Status:  MEDLINE    
The intracellular serpin Proteinase Inhibitor-9 (PI-9) is a potent inhibitor of the cytotoxic lymphocyte (CL) proteinase granzyme B, a major effector molecule used by CLs to induce target cell apoptosis. PI-9 is produced by CLs to protect against mis-directed granzyme B. However, PI-9 expression has also been reported in immune privileged tissues. In the present study, cell-specific expression of PI-9 in placental tissue of various gestational ages was examined by immunohistochemistry. PI-9 is highly expressed by the extravillous trophoblasts that have invaded the decidua, and this high expression is maintained throughout pregnancy. Similar levels were also observed in proliferative villous cytotrophoblasts. Syncytial trophoblasts generally do not produce PI-9 to a significant level until the last few weeks of pregnancy. The villous stroma contains mixed populations of PI-9 positive and negative cells throughout pregnancy, with highest expression during the second trimester. Compared to first trimester placentas, syncytial trophoblasts of partial and complete hydatidiform moles showed marked up-regulation of PI-9. Examination of choriocarcinoma cell lines also demonstrated a very high level of PI-9 is produced by these cells, which may provide protection from granzyme B-mediated apoptosis. The cell-specific expression of PI-9 in the placenta is consistent with a function in the maintenance of immune privilege, and it is proposed that up-regulated expression of PI-9 in gestational trophoblastic diseases contributes to disease pathogenesis via immune evasion.
M S Buzza; P Hosking; P I Bird
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-26
Journal Detail:
Title:  Placenta     Volume:  27     ISSN:  0143-4004     ISO Abbreviation:  Placenta     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-11-28     Completed Date:  2006-02-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  England    
Other Details:
Languages:  eng     Pagination:  62-9     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Monash University, Australia.
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MeSH Terms
Carcinoma / metabolism
Cell Line
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic*
Hydatidiform Mole / embryology,  metabolism*,  pathology
Neoplasm Proteins / metabolism*
Placenta / metabolism,  pathology
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / metabolism*
Serpins / metabolism*
Reg. No./Substance:
0/Neoplasm Proteins; 0/SERPINA9 protein, human; 0/Serine Proteinase Inhibitors; 0/Serpins; EC 3.4.21.-/GZMB protein, human; EC 3.4.21.-/Granzymes; EC 3.4.21.-/Serine Endopeptidases

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