scholarly journals Localization of Indoleamine 2,3-Dioxygenase-1 and Indoleamine 2,3-Dioxygenase-2 at the Human Maternal-Fetal Interface

2020 ◽  
Vol 13 ◽  
pp. 117864692098416
Author(s):  
Yoshiki Kudo ◽  
Iemasa Koh ◽  
Jun Sugimoto
Keyword(s):  
Interferon Γ ◽  
Kynurenine Pathway ◽  
Explant Culture ◽  
Immunohistochemical Localization ◽  
Tryptophan Metabolism ◽  
Indoleamine 2,3 Dioxygenase ◽  
Cellular Expression ◽  
Normal Human ◽  
Protein Immunoreactivity ◽  
Maternal Fetal Interface

Immunohistochemical localization of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, the first and rate-limiting enzyme in tryptophan metabolism along the kynurenine pathway, has been studied in order to better understand the physiological significance of these enzymes at the maternal-fetal interface of human pregnancy with a gestational age of 7 weeks (n = 1) and term placentas (37-40 weeks of gestation, n = 5). Indoleamine 2,3-dioxygenase-1 protein immunoreactivity was found in glandular epithelium of the decidua and the endothelium of the fetal blood vessels in the villous stroma with some additional positive cells in the villous core and in the decidua. The syncytiotrophoblast stained strongly for indoleamine 2,3-dioxygenase-2. Immunoreactivity of kynurenine, the immediate downstream product of indoleamine 2,3-dioxygenase-mediated tryptophan metabolism, showed the same localization as that of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, suggesting these are functional enzymes. Interferon-γ added to placental villous explant culture markedly stimulated expression level of both mRNA and immunoreactivity of indoleamine 2,3-dioxygenase-1. The different cellular expression and interferon-γ sensitivity of these enzymes at the maternal-fetal interface suggests distinct physiological roles for each enzyme in normal human viviparity.

Immunohistochemical localization of interferon-γ in normal human ovary

1994 ◽  
Vol 8 (3) ◽  
pp. 161-168 ◽  
Author(s):  
G. Grasso ◽  
A. Asano ◽  
T. Minagawa ◽  
T. Tanaka ◽  
S. Fujimoto ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Immunohistochemical Localization ◽  
Human Ovary ◽  
Normal Human

scholarly journals Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types

1997 ◽  
Vol 326 (2) ◽  
pp. 351-356 ◽  
Author(s):  
Melvyn P. HEYES ◽  
Cai Y. CHEN ◽  
Eugene O. MAJOR ◽  
Kuniaki SAITO
Keyword(s):  
Quinolinic Acid ◽  
Fetal Brain ◽  
Cell Types ◽  
Interferon Γ ◽  
Kynurenine Pathway ◽  
Human Cells ◽  
Hydroxylase Activity ◽  
Human Fetal Brain ◽  
Indoleamine 2,3 Dioxygenase ◽  
A Cell

Substantial increases in the tryptophan–kynurenine pathway metabolites, L-kynurenine and the neurotoxin quinolinic acid, occur in human brain, blood and systemic tissues during immune activation. Studies in vitrohave shown that not all human cells are capable of synthesizing quinolinate. To investigate further the mechanisms that limit L-kynurenine and quinolinate production, the activities of kynurenine pathway enzymes and the ability of different human cells to convert pathway intermediates into quinolinate were compared. Stimulation with interferon γ substantially increased indoleamine 2,3-dioxygenase activity and L-kynurenine production in primary peripheral blood macrophages and fetal brains (astrocytes and neurons), as well as cell lines derived from macrophage/monocytes (THP-1), U373MG astrocytoma, SKHEP1 liver and lung (MRC-9). High activities of kynurenine 3-hydroxylase, kynureninase or 3-hydroxyanthranilate 3,4-dioxygenase were found in interferon-γ-stimulated macrophages, THP-1 cells and SKHEP1 cells, and these cells made large amounts of quinolinate when supplied with L-tryptophan, L-kynurenine, 3-hydroxykynurenine or 3-hydroxyanthranilate. Quinolinate production by human fetal brain cultures and U373MG cells was restricted by the low activities of kynurenine 3-hydroxylase, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase, and only small amounts of quinolinate were synthesized when cultures were supplied with L-tryptophan or 3-hydroxyanthranilate. In MRC-9 cells, quinolinate was produced only from 3-hydroxykynurenine and 3-hydroxyanthranilate, consistent with their low kynurenine 3-hydroxylase activity. The results are consistent with the notion that indoleamine 2,3-dioxygenase is an important regulatory enzyme in the production of L-kynurenine and quinolinate. Kynurenine 3-hydroxylase and, in some cells, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase are important determinants of whether a cell can make quinolinate.

scholarly journals What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Yu Yao ◽  
Heng Liang ◽  
Xin Fang ◽  
Shengnan Zhang ◽  
Zikang Xing ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Kynurenine Pathway ◽  
Phase Iii ◽  
Current Status ◽  
The Past ◽  
Indoleamine 2,3 Dioxygenase ◽  
Negative Results ◽  
Rate Limiting Step ◽  
Pharmacodynamic Markers ◽  
Tumor Types

AbstractIndoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.

scholarly journals Immunohistochemical localization of periostin in human gingiva

2015 ◽  
Vol 59 (3) ◽  
Author(s):  
T. Cobo ◽  
A. Obaya ◽  
S. Cal ◽  
L. Solares ◽  
R. Cabo ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Western Blot ◽  
Protein Band ◽  
Immunohistochemical Localization ◽  
Matricellular Protein ◽  
Double Immunofluorescence ◽  
Periodontal Tissues ◽  
Human Gingiva ◽  
Normal Human ◽  
Bidirectional Interactions

<p>The periostin is a matricellular protein expressed in collagen-rich tissues including some dental and periodontal tissues where it is regulated by mechanical forces, growth factors and cytokines. Interestingly the expression of this protein has been found modified in different gingival pathologies although the expression of periostin in normal human gingiva was never investigated. Here we used Western blot and double immunofluorescence coupled to laser-confocal microscopy to investigated the occurrence and distribution of periostin in different segments of the human gingival in healthy subjects. By Western blot a protein band with an estimated molecular mass of 94 kDa was observed. Periostin was localized at the epithelial-connective tissue junction, or among the fibers of the periodontal ligament, and never co-localized with cytokeratin or vimentin thus suggesting it is an extracellular protein. These results demonstrate the occurrence of periostin in adult human gingiva; its localization suggests a role in the bidirectional interactions between the connective tissue and the epithelial cells, and therefore in the physiopathological conditions in which these interactions are altered.  </p>

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