The Etiological Role of Allogeneic Fetal Rejection in Pre‐Eclampsia

Nishizawa, Haruki; Hasegawa, Kiyoshi; Suzuki, Manami; Kamoshida, Shingo; Kato, Takema; Tsutsumi, Yutaka; Kurahashi, Hiroki; Udagawa, Yasuhiro

doi:10.1111/j.1600-0897.2007.00484.x

Cited by 35 publications

(40 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present results regarding ido expression are consistent with previous reports describing a relationship between ido and the pathogenesis of preeclampsia (6). in agreement with this study, nishizawa et al (5) demonstrated that placental IDO activity values had a significant inverse correlation with both systolic and diastolic blood pressure, indicating that the severity of preeclampsia is inversely correlated with ido activity. The mechanism of ido-mediated immunosuppression was initially believed to depend on the inhibition of T-cell effectors by toxic metabolites of tryptophan (26).…”

Section: Discussionsupporting

confidence: 83%

“…although it is a common disease, its pathogenesis has yet to be fully elucidated. increasing evidence now indicates that this disorder may have an immunological cause, in the form of allogeneic fetal rejection (3)(4)(5). in recent years, the down-regulation of indoleamine 2,3-dioxygenase (ido) and diminished regulatory T cells (Tregs) in preeclampsia have been separately reported to play a crucial role in the maladaptation of maternal tolerance and the pathogenesis of preeclampsia (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced expression of indoleamine 2,3-dioxygenase participates in pathogenesis of preeclampsia via regulatory T cells

Liu

Ding

et al. 2010

Mol Med Rep

View full text Add to dashboard Cite

Abstract. Preeclampsia is a complex multi-organ disease and the leading cause of maternofetal morbidity and mortality. low levels of indoleamine 2,3-dioxygenase (ido) and diminished numbers of regulatory T cells (Tregs) have been separately reported to participate in the pathogenesis of preeclampsia. in the present study, we aimed to determine whether alterations in the expression of ido, forkhead box P3 (Foxp3) and interleukin-18 (il-18) contribute to the pathogenesis of preeclampsia, by measuring their levels in preeclamptic placentae and in placentae from healthy pregnant women as a control. ido protein levels were determined by immunohistochemistry, while the mrna levels of ido, FoxP3 and il-18 were measured by quantitative rT-Pcr. The intensity of ido immunostaining was lower in the preeclamptic placentae than in the normal controls, and was related to the clinical severity of the preeclampsia. Quantitative rT-Pcr revealed that the ido and il-18 mrna levels were reduced in a correlated manner the preeclamptic placentae compared to the controls, and that the levels of FoxP3 mrna were consistently decreased in the preeclamptic group. a positive correlation betwen FoxP3 and ido mrna was found. The results of the study indicate that il-18, ido and FoxP3 mrna levels were decreased in the preeclamptic placentae. reduced ido levels in pre eclampsia may be partly influenced by IL-18, and result in the maladaptation of maternal tolerance and the pathogenesis of preeclampsia by directly reducing Tregs.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Reduced expression of indoleamine 2,3-dioxygenase participates in pathogenesis of preeclampsia via regulatory T cells

Liu

Ding

et al. 2010

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…1A) [Nishizawa et al 2007]. To study the effects of IDO as an antioxidant, we examined the levels of placental 8-OHdG, a well established marker of oxidative damage to DNA.…”

Section: Resultsmentioning

confidence: 99%

“…We previously demonstrated that indoleamine 2,3-dioxygenase (IDO) enzymatic activity is significantly reduced in pre-eclamptic placentas [Nishizawa et al 2007]. IDO is the initial and rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan in macrophages, dendritic cells, and trophoblasts in placental villi.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients

Nishizawa¹,

Suzuki²,

Pryor-Koishi³

et al. 2011

Systems Biology in Reproductive Medicine

Self Cite

View full text Add to dashboard Cite

Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan, but a wider range of functions have now been proposed for this enzyme, including antioxidant activity. Our previous study revealed that reduced IDO expression in the placenta induces defective feto-maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present study, we assessed the effects of low placental IDO activity as an antioxidant. The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for oxidative damage to DNA, were significantly higher in pre-eclamptic than normotensive pregnancies (P < 0.05). Immunohistochemical signals of 8-OHdG were detected mainly in syncytiotrophoblasts and vascular endothelial cells, and colocalized with those for IDO. Furthermore, a significant inverse correlation was found between the IDO activity and 8-OhdG levels. These results show that oxidative stress is associated with decreased IDO activity in the pre-eclamptic placenta and suggest an impact of low IDO activity other than immune modulation in promoting the onset of this disorder.

show abstract

Efficient tryptophan‐catabolizing activity is consistently conserved through evolution of TDO enzymes, but not IDO enzymes

Yuasa

Ball

2015

J Exp Zool Pt B

View full text Add to dashboard Cite

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. TDO is found in almost all metazoan and many bacterial species, but not in fungi. We show that TDO enzymes have high catalytic-efficiency for L-Trp catabolism, regardless of their biological origin, suggesting that TDO has been an L-Trp-specific degrading enzyme throughout its evolution. Meanwhile, IDO was initially discovered in mammals, and subsequently has been found in lower vertebrates, several invertebrates, fungi and a number of bacterial species. Some lineages have independently generated multiple IDO paralogues through gene duplications. Interestingly, only mammalian IDO1s and fungal "typical" IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. We show that invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. We suggest that the phylogenetic distribution of "low catalytic-efficiency IDOs" indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp-catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic-efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species. Investigation of other substrates and functions of the ancestral IDO and low catalytic efficiency IDOs may identify additional biological roles for these enzymes.

show abstract

The Etiological Role of Allogeneic Fetal Rejection in Pre‐Eclampsia

Abstract: Our findings implicate a potential role for IDO activity and a maternal immunological reaction against an allogeneic fetus in the etiology of pre-eclampsia.

Cited by 35 publications

References 34 publications

Reduced expression of indoleamine 2,3-dioxygenase participates in pathogenesis of preeclampsia via regulatory T cells

Reduced expression of indoleamine 2,3-dioxygenase participates in pathogenesis of preeclampsia via regulatory T cells

Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients

Efficient tryptophan‐catabolizing activity is consistently conserved through evolution of TDO enzymes, but not IDO enzymes

Contact Info

Product

Resources

About