ABSTRACT
CBA/JXDBA/2J murine abortion is known to be associated with increased local and peripheral Th1-cytokines levels. The role of the pro-inflammatory interleukin-6 (IL-6) in murine abortion remains unclear. In humans, IL-6 was reported to be elevated at the onset of spontaneous abortion. The aim of our study was to evaluate the levels of IL-6 during murine pregnancy in (1) the normal murine pregnancy combination CBA/JXBALB/c and in (2) the CBA/JXDBA/2J abortion prone mating combination. We measured IL-6 serum levels by ELISA and local (placental and decidual) IL-6 levels by flow cytometry and immunohistochemistry. The expression of the IL-6 receptor gp80 was further analyzed. We additionally evaluated the number of mast cells and macrophages at the feto-maternal interface as a putative IL-6 source in reproductive tissues. IL-6 and gp80 were expressed in decidual cells as well as in different trophoblast types. Flow cytometry analysis showed increased numbers of IL-6+ cells in abortion placentas and deciduas compared to control pregnant mice. We observed an elevated number of mast cells and macrophages at the feto-maternal interface from abortion mice in comparison to control mice. Interestingly, we found very high numbers of mast cells, macrophages and IL-6+ cells in resorption tissue compared to control tissues. Flow cytometry studies confirmed that macrophages are being an important source of IL-6 at the feto-maternal interface. The mRNA IL-6 levels were also enhanced in placenta and decidua from mice with high abortion rate compared to normal pregnant mice, as analyzed by RT-PCR. Our results suggest that IL-6 produced not only by immunocompetent cells such as macrophages and mast cells, but also by trophoblasts and decidua cells, is directly involved in the pathology of abortion.
Subject(s)
Abortion, Veterinary/metabolism , Decidua/metabolism , Interleukin-6/metabolism , Placenta/metabolism , Abortion, Veterinary/genetics , Abortion, Veterinary/pathology , Animals , CD11b Antigen/analysis , Cell Count , Crosses, Genetic , Decidua/chemistry , Decidua/pathology , Female , Fetal Resorption/genetics , Fetal Resorption/metabolism , Fetal Resorption/pathology , Flow Cytometry , Gene Expression , Immunohistochemistry , Interleukin-6/blood , Interleukin-6/genetics , Macrophages/cytology , Male , Mast Cells/cytology , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Mice, Inbred DBA , Monocytes/metabolism , Placenta/chemistry , Placenta/pathology , Pregnancy , Receptors, Interleukin-6/metabolism , Trophoblasts/chemistryABSTRACT
Inmunopatología
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