HDAC-mediated repression of IFN-γ responses is conserved in mouse and human trophoblast cells (166.20)
| Autor: | Shawn Murphy, Danielle Sullivan, Paige Weise, Jason Choi, Meghan Bushway |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:166.20-166.20 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.166.20 |
| Popis: | Successful pregnancy requires that the semi-allogeneic conceptus evades maternal immune-mediated rejection, while the maternal immune system simultaneously protects mother and fetus from infection. IFN-γ is a pro-inflammatory cytokine that activates innate and adaptive immunity, induces apoptosis and inhibits cell proliferation. During normal pregnancy, IFN-γ is secreted in both the human and mouse uterus. Placental trophoblast cells (TBCs) are the only cells derived from the fertilized egg that contact maternal blood, and they play important roles in controlling maternal immunity to the conceptus. Human and mouse TBCs are resistant to both IFN-γ-mediated apoptosis and activation of MHC class II expression. Moreover, while epithelial cells can clear Toxoplasma infections when exposed to IFN-γ, TBCs cannot. These collective results suggest that TBCs are resistant to IFN-γ. We recently demonstrated that IFN-γ-inducible gene expression is inhibited in mouse TBCs by histone deactylases (HDACs). Our current studies utilizing selective HDAC inhibitors and siRNA suggest that HDAC-2 and/or -3 are responsible for repressing IFN-γ-inducible gene expression in mouse TBCs. Importantly, HDAC-mediated repression of IFN-γ responses is conserved in Jar human TBC-derived choriocarcinoma cells. In contrast, HDACs activate these same genes in human cells of non-trophoblastic origin. These collective results suggest that HDACs function by a novel mechanism to repress IFN-γ-responses in TBCs. |
| Databáze: | OpenAIRE |
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