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Publication : Mifepristone (Ru486) antagonizes monocyte chemotactic protein-3 down-regulation at early mouse pregnancy revealing immunomodulatory events in Ru486 induced abortion.

First Author  Nautiyal J Year  2004
Journal  Am J Reprod Immunol Volume  52
Issue  1 Pages  8-18
PubMed ID  15214937 Mgi Jnum  J:91313
Mgi Id  MGI:3046473 Doi  10.1111/j.1600-0897.2004.00176.x
Citation  Nautiyal J, et al. (2004) Mifepristone (ru486) antagonizes monocyte chemotactic protein-3 down-regulation at early mouse pregnancy revealing immunomodulatory events in ru486 induced abortion. Am J Reprod Immunol 52(1):8-18
abstractText  Nautiyal J, Kumar PG, Laloraya M. Mifepristone (Ru486) antagonizes Monocyte Chemotactic Protein-3 down-regulation at early mouse pregnancy revealing immunomodulatory events in Ru486 induced abortion. AJRI 2004; 52:8-18 Copyright Blackwell Munksgaard, 2004Problem: The survival of an embryo bearing the paternal antigens within the immunocompetent environment of the maternal uterus renders 'pregnancy' to be a state of immunological paradox. The ratio of Th1/Th2 responses is crucial for pregnancy maintenance. Monocyte Chemotactic Protein-3 (MCP3) is a pro-inflammatory, CC chemokine and a Th1 effector which is capable of eliciting significant anti-tumoral immune responses. Method of study: MCP3 expression was investigated in the murine uterine tissue at different days of initial pregnancy and the effect of RU 486 in immature and delayed implantation model studied using Western blotting and Immunocytochemical techniques. Results and conclusion: Our results show very high uterine MCP3 expression during pre-implantation followed by a significant MCP3 down-regulation at peri-implantation and low levels of MCP3 during post-implantation period. At the peri-implantation stage, embryos exhibited lowered MCP3 expression when compared with the pre-implantation stage. Ru486, a progesterone antagonist when given in a competitive mode with progesterone resulted in a massive surge in MCP3 expression in both immature mice and delayed implantation models. We hypothesize that it is imperative for MCP3 expression to be down-regulated for the success of pregnancy. The cross-talk between Ru486 and amplified MCP3 expression may be one of the mechanisms by way of which RU486 performs its abortificient and anti tumor role.
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