Indoleamine 2,3-dioxygenase (IDO) activity in placental compartments of renal-transplanted pregnant women.
OBJECTIVE
Immunosuppressive drugs change gestational IDO activity at the maternal-fetal interface.


METHODS
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.


CONCLUSIONS
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.
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Karen Matias
KM
do Prado
Simone
S
Correa-Silva
Leandro Gustavo
LG
Oliveira
Niels Olsen Saraiva
NO
Camara
Erica
E
Ono
Silvana
S
Sandri
Melissa Cavalheiro
MC
Tourino
Ana
A
Campa
Larissa
L
de Sá Lima
Cristoforo
C
Scavone
Estela
E
Bevilacqua
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D016030:Kidney Transplantation; D016328:NF-kappa B / Q000096:biosynthesis; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D007371:Interferon-gamma
IDO; IFN-γ; Immunosuppressive drugs; Kynurenine; NF-κB; Placenta