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Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia

Keaton, Sarah A. ; Heilman, Patrick ; Bryleva, Elena Y. ; Madaj, Zachary ; Krzyzanowski, Stanislaw ; Grit, Jamie ; Miller, Emily S. ; Jälmby, Maya LU ; Kalapotharakos, Grigoros and Racicot, Karen , et al. (2019) In International Journal of Tryptophan Research 12.
Abstract

Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin... (More)

Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.

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publication status
published
subject
keywords
indoleamine 2,3-dioxygenase, kynurenine pathway, pre-eclampsia, serum amyloid A, tryptophan, tryptophan 2,3-dioxygenase
in
International Journal of Tryptophan Research
volume
12
publisher
Libertas Academica
external identifiers
  • scopus:85069612092
ISSN
1178-6469
DOI
10.1177/1178646919840321
language
English
LU publication?
yes
id
d5df9904-9e97-4fd0-a249-2250658d74b2
date added to LUP
2021-02-12 09:35:38
date last changed
2022-04-27 00:11:52
@article{d5df9904-9e97-4fd0-a249-2250658d74b2,
  abstract     = {{<p>Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.</p>}},
  author       = {{Keaton, Sarah A. and Heilman, Patrick and Bryleva, Elena Y. and Madaj, Zachary and Krzyzanowski, Stanislaw and Grit, Jamie and Miller, Emily S. and Jälmby, Maya and Kalapotharakos, Grigoros and Racicot, Karen and Fazleabas, Asgerally and Hansson, Stefan R. and Brundin, Lena}},
  issn         = {{1178-6469}},
  keywords     = {{indoleamine 2,3-dioxygenase; kynurenine pathway; pre-eclampsia; serum amyloid A; tryptophan; tryptophan 2,3-dioxygenase}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Libertas Academica}},
  series       = {{International Journal of Tryptophan Research}},
  title        = {{Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia}},
  url          = {{http://dx.doi.org/10.1177/1178646919840321}},
  doi          = {{10.1177/1178646919840321}},
  volume       = {{12}},
  year         = {{2019}},
}