title: Mechanisms regulating the expression of indoleamine 2,3-dioxygenase during decidualization of human endometrium.
abstract: BACKGROUND
  Expression of the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase, in the mouse placenta has been shown to be critical in preventing immunological rejection of the fetal allograft. To clarify the physiological importance of indoleamine 2,3-dioxygenase in human pregnancy, we have studied how the expression of this enzyme changes during decidualization of human endometrium at both the cell and tissue level.
  
  
  RESULTS
  The level of indoleamine 2,3-dioxygenase mRNA expression (determined by RT-PCR) was higher in decidual than in endometrial tissue. Uterine decidual tissue in ectopic pregnancy similarly showed increased mRNA expression. Immunohistochemistry demonstrated that indoleamine 2,3-dioxygenase protein immunoreactivity was found in glandular epithelium and in stromal cells. The intensity of this immunoreactivity was increased in decidualized tissue. In a cell culture model, the level of indoleamine 2,3-dioxygenase mRNA was suppressed specifically by progesterone-induced decidualization of isolated endometrial stromal cells. Indoleamine 2,3-dioxygenase protein abundance (determined by Western blot) was also decreased by progesterone-induced decidualization. However interferon-gamma, a potent stimulator of indoleamine 2,3-dioxygenase gene expression, increased the level of indoleamine 2,3-dioxygenase mRNA and protein in both non-decidualized and in decidualized cells. Indoleamine 2,3-dioxygenase activity (determined by measuring the concentration of tryptophan and its indoleamine 2,3-dioxygenase catabolite, kynurenine) was also decreased by progesterone-induced decidualization but enhanced following interferon-gamma treatment. Expression of other interferon-gamma inducible genes (STAT1 and tryptophanyl-tRNA synthetase) showed the same pattern as that of indoleamine 2,3-dioxygenase in tissue samples, but was not changed by decidualization in the cell culture model.
  
  
  CONCLUSIONS
  These data suggest that despite suppression by progesterone, indoleamine 2,3-dioxygenase expression in endometrial stromal cells may increase during decidualization due to stimulation by interferon-gamma secreted by infiltrating leukocytes.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. yoshkudo@hiroshima-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kudo
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Aya
authors.initials: A
authors.lastname: Toyofuku
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katsura
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Fujii
authors.forename: Koso
authors.initials: K
authors.lastname: Ohama
mesh_terms: D003656:Decidua / Q000166:cytology / Q000201:enzymology*; D004717:Endometrium / Q000166:cytology / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D011247:Pregnancy; D017154:Stromal Cells / Q000201:enzymology; D014366:Tryptophan Oxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D007371:Interferon-gamma; D014366:Tryptophan Oxygenase