Document Detail

Protection from abortion by heme oxygenase-1 up-regulation is associated with increased levels of Bag-1 and neuropilin-1 at the fetal-maternal interface.
MedLine Citation:
PMID:  16210589     Owner:  NLM     Status:  MEDLINE    
Tolerance mechanisms allowing pregnancy success resemble those involved in allograft acceptance. Heme oxygenase (HO) is a tissue-protective molecule, which allows graft acceptance and is known to have antiapoptotic effects on several cell types. We previously reported down-regulated levels of HO-1 and HO-2 in placenta from allopregnant mice undergoing abortion. In this study, we analyzed whether the up-regulation of HO-1 by cobalt-protoporphyrin (Co-PP) during implantation window can rescue mice from abortion. Induction of HO-1 by Co-PP treatment prevented fetal rejection, whereas the down-regulation of HOs by zinc-protoporphyrin application boosted abortion. The beneficial effect of HO-1 induction was not related to a local shift to Th2-profile or to a change in the NO system. Interestingly, the expression of the antiapoptotic/cytoprotective molecule Bag-1 as well as the levels of neuropilin-1, a novel marker for T regulatory cells, were up-regulated after Co-PP treatment. Our data strongly support a very important role for HO-1 in fetal allotolerance and suggest that HO-1 might be protective by up-regulating tissue protective molecules, i.e., Bag-1, and by activating T regulatory cells rather than by changing the local cytokine profile.
Andre Sollwedel; Annarosa Zambon Bertoja; Maria Laura Zenclussen; Katrin Gerlof; Ulrike Lisewski; Paul Wafula; Birgit Sawitzki; Christian Woiciechowsky; Hans-Dieter Volk; Ana Claudia Zenclussen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-07     Completed Date:  2005-12-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4875-85     Citation Subset:  AIM; IM    
Reproductive Immunology Group, Institute of Medical Immunology, Biomedizinisches Forschungszentrum (BMFZ), Charité Medical University of Berlin, Germany.
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MeSH Terms
Abortion, Spontaneous / metabolism*,  prevention & control
Biological Markers
Carrier Proteins / metabolism*
DNA-Binding Proteins
Heme Oxygenase-1 / physiology*
Maternal-Fetal Exchange / physiology*
Mice, Inbred BALB C
Mice, Inbred CBA
Mice, Inbred DBA
Neuropilin-1 / metabolism*
Nitric Oxide Synthase Type II / biosynthesis,  genetics
Nitric Oxide Synthase Type III / biosynthesis,  genetics
Protoporphyrins / pharmacology
T-Lymphocytes, Regulatory / metabolism
Th2 Cells / metabolism
Transcription Factors
Up-Regulation / physiology
Reg. No./Substance:
0/BCL2-associated athanogene 1 protein; 0/Biological Markers; 0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Protoporphyrins; 0/Transcription Factors; 14325-03-2/cobaltiprotoporphyrin; 144713-63-3/Neuropilin-1; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC Oxygenase-1

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