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1.  Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity 
Background
Mesenchymal stem cells (MSCs) are increasingly considered to be used as biological immunosuppressants in hematopoietic stem cell transplantation (HSCT). In the early reconstitution phase following HSCT, natural killer (NK) cells represent the major lymphocyte population in peripheral blood and display graft-vs-leukemia (GvL) effects. The functional interactions between NK cells and MSCs have the potential to influence the leukemia relapse rate after HSCT. Until date, MSC-NK cell interaction studies are largely focussed on bone marrow derived (BM)-MSCs. Umbilical cord derived (UC)-MSCs might be an alternative source of therapeutic MSCs. Thus, we studied the interaction of UC-MSCs with unstimulated allogeneic NK cells.
Results
UC-MSCs could potently suppress NK cell cytotoxicity in overnight cultures via soluble factors. The main soluble immunosuppressant was identified as prostaglandin (PG)-E2. Maximal PGE2 release involved IL-1β priming of MSCs after close contact between the NK cells and UC-MSCs. Interestingly, blocking gamma-secretase activation alleviated the immunosuppression by controlling PGE2 production. IL-1 receptor activation and subsequent downstream signalling events were found to require gamma-secretase activity.
Conclusion
Although the role of PGE2 in NK cell-MSC has been reported, the requirement of cell-cell contact for PGE2 induced immunosuppression remained unexplained. Our findings shed light on this puzzling observation and identify new players in the NK cell-MSC crosstalk.
Electronic supplementary material
The online version of this article (doi:10.1186/s12964-014-0063-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12964-014-0063-9
PMCID: PMC4195898  PMID: 25266361
UC-MSC; NK cell cytotoxicity; Immunosuppression; IL-1β; Gamma-secretase
2.  HIV-1 and SUMOylation 
Retrovirology  2013;10(Suppl 1):P106.
doi:10.1186/1742-4690-10-S1-P106
PMCID: PMC3847840
4.  PIAS3 modulate HIV-1 integrase SUMOylation 
Retrovirology  2011;8(Suppl 2):P4.
doi:10.1186/1742-4690-8-S2-P4
PMCID: PMC3236928
5.  Highly Ordered Spatial Organization of the Structural Long Noncoding NEAT1 RNAs within Paraspeckle Nuclear Bodies 
Molecular Biology of the Cell  2010;21(22):4020-4027.
We describe the spatial organization of the two NEAT1 noncoding (nc)RNAs required for the integrity of the paraspeckle nuclear bodies. The central sequences of the long transcript are internal when its extremities and the short isoform are peripheral, indicating how RNA can contribute to the architecture of nuclear bodies.
Paraspeckles (PSPs) are nuclear bodies associated with the retention in the nucleus of specific mRNAs. Two isoforms of a long noncoding RNA (NEAT1_v1/Menε and NEAT1_v2/Menβ) are required for the integrity of PSPs. Here, we analyzed the molecular organization of PSPs by immuno- and in situ hybridization electron microscopy. Detection of the paraspeckle markers PSPC1 and P54NRB/NONO confirm the identity between PSPs and the previously described interchromatin granule-associated zones (IGAZs). High-resolution in situ hybridization of NEAT1 transcripts revealed a highly ordered organization of IGAZ/PSPs. Although the 3.7-kb NEAT1_v1 and the identical 5′ end of the 22.7-kb NEAT1_v2 transcripts are confined to the periphery, central sequences of NEAT1_v2 are found within the electron-dense core of the bodies. Moreover, the 3′ end of NEAT1_v2 also localize to the periphery, indicating possible architectures for IGAZ/PSPs. These results further suggest that the organization of NEAT1 transcripts constrains the geometry of these bodies. Accordingly, we observed in HeLa and NIH 3T3 cells that IGAZ/PSPs are elongated structures with a well-defined diameter. Our results provide new insight on the ability of noncoding RNAs to form subcellular structures.
doi:10.1091/mbc.E10-08-0690
PMCID: PMC2982136  PMID: 20881053

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