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Am J Reprod Immunol. 2011 Sep;66(3):209-22. doi: 10.1111/j.1600-0897.2011.00986.x. Epub 2011 Mar 9.

Peptidoglycan induces necrosis and regulates cytokine production in murine trophoblast stem cells.

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  • 1Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO 63110, USA.

Abstract

PROBLEM:

Intrauterine bacterial infection during pregnancy may lead to adverse outcome. The objective of this study was to assess whether peptidoglycan (PGN) derived from Gram-positive bacteria induces trophoblast stem (TS) cell death or alters TS cell cytokine production.

METHOD OF STUDY:

Toll-like receptor (TLR) transcript expression was assessed by RT-PCR. Protein expression was determined by confocal microscopy or flow cytometry. 7-Aminoactinomycin D (7-AAD) staining was used to assess TS cell death. Morphological features of cell death were evaluated by transmission electron microscopy. The presence of cleaved caspase-3 and high mobility group box 1 (HMGB1) protein was examined by Western blot. Cytokine levels in cell supernatants were determined using a mouse cytokine 23-plex panel.

RESULTS:

Toll-like receptor 2 and TLR4 protein was expressed from the 1-cell stage through the blastocyst stage of murine embryo development. Murine TS cells expressed TLR2 and TLR6 but not TLR1 or TLR4 RNA. Only TLR2 protein was detected at the plasma membrane of TS cells. PGN induced TS cell death by a caspase-3-independent mechanism. The cell death pathway induced by PGN was morphologically consistent with necrosis. Finally, PGN induced HMGB1 release and increased MIP-1β secretion while inhibiting the constitutive release of RANTES.

CONCLUSION:

Peptidoglycan-induced TS cell necrosis and the subsequent release of HMGB1 and MIP-1β may regulate an infection-induced inflammatory response at the maternal-fetal interface and thus may play a role in the pathogenesis of infection-associated pregnancy complications.

© 2011 John Wiley & Sons A/S.

PMID:
21385270
[PubMed - indexed for MEDLINE]
PMCID:
PMC3137696
Free PMC Article
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