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221.
VM Abrahams PB Aldo R Romero G Mor 《American journal of reproductive immunology (New York, N.Y. : 1989)》2006,55(6):390-391
Introduction: Increased trophoblast apoptosis has been observed in pregnancy complications such as preeclampsia. The factors promoting this cell death are unknown. Trophoblasts express Toll-like receptors (TLR), enabling them to recognize microorganisms. In response to the TLR2 ligand peptidoglycan (PDG), trophoblasts undergo apoptosis suggesting that gram-positive bacteria may promote trophoblast apoptosis. The objective of this study was to characterize the cellular mechanism by which TLR2 induces apoptosis. We report the role of TLR6 in the regulation of TLR2 mediated apoptosis following ligation by PDG.
Methods: First trimester trophoblast cell lines express TLR1 and TLR2 but lack TLR6 and are sensitive to PDG-mediated apoptosis. Three stable transfectants were made to express either a TLR1 dominant negative (TLR1-DN), a TLR2 dominant negative (TLR2-DN) or full length TLR6. Cells were treated with PDG (40 μg/mL) after which cell viability, caspase-3 activity and cytokine production were evaluated.
Results: Trophoblasts expressing the TLR2-DN showed a 57.4 ± 1.2% inhibition in PDG-induced caspase-3 activity compared with wildtype cells, while the TLR1-DN inhibited PDG-induced caspase-3 activity by 61.6 ± 1.1%. Expression of TLR6 by trophoblasts, reversed PDG-mediated apoptosis as shown by reduced caspase-3 activity (77.6 ± 1.2%) and increased cytokine production.
Conclusion: These results suggest that a gram-positive bacterial infection during pregnancy may promote trophoblast apoptosis via TLR2/TLR1 heterodimers. Expression of TLR6, however, may protect the trophoblast from PDG-induced apoptosis and instead promote an inflammatory response. These findings shed new light on the mechanisms by which infection may affect placental function and pregnancy outcome. 相似文献
Methods: First trimester trophoblast cell lines express TLR1 and TLR2 but lack TLR6 and are sensitive to PDG-mediated apoptosis. Three stable transfectants were made to express either a TLR1 dominant negative (TLR1-DN), a TLR2 dominant negative (TLR2-DN) or full length TLR6. Cells were treated with PDG (40 μg/mL) after which cell viability, caspase-3 activity and cytokine production were evaluated.
Results: Trophoblasts expressing the TLR2-DN showed a 57.4 ± 1.2% inhibition in PDG-induced caspase-3 activity compared with wildtype cells, while the TLR1-DN inhibited PDG-induced caspase-3 activity by 61.6 ± 1.1%. Expression of TLR6 by trophoblasts, reversed PDG-mediated apoptosis as shown by reduced caspase-3 activity (77.6 ± 1.2%) and increased cytokine production.
Conclusion: These results suggest that a gram-positive bacterial infection during pregnancy may promote trophoblast apoptosis via TLR2/TLR1 heterodimers. Expression of TLR6, however, may protect the trophoblast from PDG-induced apoptosis and instead promote an inflammatory response. These findings shed new light on the mechanisms by which infection may affect placental function and pregnancy outcome. 相似文献
222.
Clonogenicity of circulating neuroblastoma cells: implications regarding peripheral blood stem cell transplantation 总被引:1,自引:0,他引:1
Peripheral blood stem cells (PBSCs) are being used as an alternative to autologous marrow rescue for hematopoietic reconstitution after high- dose chemotherapy in patients with neuroblastoma and other solid malignancies. Use of PBSCs is preferred by some because of the belief that there is less risk of tumor contamination. Because tumor stem cell contamination is thought to be one contributing cause of relapse after myeloablative therapy and autologous reconstitution, we examined the potential risk of reinfusing circulating neuroblastoma cells by in vitro evaluation of their clonogenicity. Immunocytologic and tumor cell clonogenic analyses were performed on 74 blood samples obtained from 56 children with advanced-stage neuroblastoma. Concurrently drawn bone marrow specimens were evaluated in 30 instances. Circulating neoplastic cells were detected in 19 of 74 (26%) for all specimens and by immunologic techniques (26%). Using a clonogenic assay, 13 grew identifiable tumor colonies. Comparing results with the two techniques showed tumor colony growth in 10 of the 19 positive specimens by immunocytology. However, 3 of 53 samples (6%) that were negative by immunocytology were positive by the clonogenic assay. Of the 11 positive blood samples, 9 concurrent marrows contained neuroblastoma cells; of the 19 negative blood specimens, 3 concurrent marrows had metastatic disease. We conclude that circulating neuroblastoma cells are present in peripheral blood and have clonogenic properties in vitro. This supports the view that tumor cell contamination may well be one cause of relapse after autologous reconstitution. Consequently, PBSC collections should also undergo meticulous monitoring for tumor contamination before autologous reinfusion. 相似文献
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