Indoleamine 2,3-dioxygenase (IDO) Activity in Placental Compartments of Renal-Transplanted Pregnant Women

Authors

  • Karen Matias do Prado,

    1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Simone Correa-Silva,

    1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
    2. Post-graduate Program in Gynecology Obstetrics and Mastology, Botucatu Medical School, UNESP – São Paulo State University, Botucatu, Brazil
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  • Leandro Gustavo Oliveira,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Niels Olsen Saraiva Camara,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Érica Ono,

    1. Department of Pediatrics, School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
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  • Silvana Sandri,

    1. Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Melissa Cavalheiro Tourino,

    1. Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Ana Campa,

    1. Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Larissa de Sá Lima,

    1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Cristoforo Scavone,

    1. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Estela Bevilacqua

    Corresponding author
    1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
    • Correspondence

      Estela Bevilacqua, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes, 1524 – Butantan - 05508-000 SP-SP Brazil.

      E-mail: bevilacq@usp.br

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Abstract

Problem

Immunosuppressive drugs change gestational IDO activity at the maternal–fetal interface.

Method of Study

Analysis of placental IDO expression and activity, interferon gamma (IFN-γ), and IL-10 expression and NFkB activity in renal transplant recipient women under immunosuppressive treatment.

Results

We demonstrated a significant reduction in IDO activity (P = 0.0275) and expression (P = 0.026) and in NFkB activity (P = 0.0176) in the villous region of renal transplanted mother. These findings did not correlate with the higher serum levels of kynurenine (P = 0.002). In the decidual compartment, IDO was immunolocalized mainly on the extravillous cytotrophoblast but did not show significant differences among the experimental groups; kynurenine was significantly higher (P = 0.036) and was inversely proportional to the decidual IFN-γ profile (P = 0.0433). No change was seen in IL-10 levels. NFkB activity was significantly higher in decidual compartment correlating with the higher IDO activity and suggesting that in immunosuppressant pregnancy, IDO activity and expression remain regulated by NFkB.

Conclusion

The increased IDO activity in decidua may indicate an attempt to offset the low expression. These findings call attention to the relevance of IDO activity at the maternal interface in pregnant transplant recipients, likely modulated by immunosuppressive agents and associated with a high risk of associated gestational disorders.

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