Keaton Sarah A, Heilman Patrick, Bryleva Elena Y, Madaj Zachary, Krzyzanowski Stanislaw, Grit Jamie, Miller Emily S, Jälmby Maya, Kalapotharakos Grigoros, Racicot Karen, Fazleabas Asgerally, Hansson Stefan R, Brundin Lena
Department of Physiology, Michigan State University, East Lansing, MI, USA.
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
Int J Tryptophan Res. 2019 Apr 8;12:1178646919840321. doi: 10.1177/1178646919840321. eCollection 2019.
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.
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.
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.
分解色氨酸的犬尿氨酸途径酶在胎盘组织中含量丰富。这些代谢产物参与免疫调节机制，尽管该途径在子痫前期（PE）中的作用才刚刚开始被阐明。在此，我们测定了患有和未患有PE的女性胎盘组织中色氨酸和代谢产物水平，以及犬尿氨酸途径酶和炎症因子的表达。
分析了36个胎盘（18个PE胎盘和18个对照胎盘）中犬尿氨酸途径酶吲哚胺-2,3-双加氧酶（IDO1和2）、色氨酸-2,3-双加氧酶（TDO）、犬尿氨酸-3-单加氧酶（KMO）和喹啉酸磷酸核糖基转移酶（QPRT）以及白细胞介素（IL）-1β、IL-6和血清淀粉样蛋白A（SAA）的表达。使用高压液相色谱法测量色氨酸和犬尿氨酸含量，使用气相色谱-质谱法测量喹啉酸含量。
患有PE的女性胎盘组织中色氨酸含量降低。患有PE的女性胎盘组织中犬尿氨酸/色氨酸比值升高，但下游代谢产物无显著变化。我们证实患有PE的女性胎盘组织中IDO1表达降低，TDO表达出现代偿性增加。与对照组相比，PE胎盘组织中SAA降低。我们的数据表明，患有PE的女性胎盘组织中色氨酸含量和炎症介质SAA均受到影响。有必要进一步研究色氨酸分解代谢和炎症介质在维持胎盘健康免疫生物学途径中的作用。
