Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule

Huang, Guanyou; Zeng, Yao-Ying; Liang, Ping; Congrong, Zhou; Zhao, Shuyun; Huang, Xiuyan; Wu, Ling-Fei; He, Xuan

doi:10.3390/ijms130910863

Cited by 9 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The pcDNA6.2-GW/EmGFP-GRP78-siR plasmid and pcDNA6.2-GW/EmGFP-Caspase-4-siR plasmid vectors were constructed as previously described [ 40 ]. Briefly, for pcDNA6.2-GW/EmGFP-GRP78- siR, four siRNA candidate sequences targeting GRP78 (GRP78-1 to GRP78-4) were cloned into pcDNA6.2-GW/emerald green fluorescent protein (GFP) vector.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Antitumor Effects of Adenoviral-Mediated siRNA against GRP78 Gene on Adenosine-Induced Apoptosis in Human Hepatoma HepG2 Cells

Guo

Zhang

et al. 2014

IJMS

View full text Add to dashboard Cite

Our previous studies show that adenosine-induced apoptosis is involved in endoplasmic reticulum stress in HepG2 cells. In this study, we have investigated whether knockdown of GRP78 by short hairpin RNA (shRNA) increases the cytotoxic effects of adenosine in HepG2 cells. The adenovirus vector-delivered shRNA targeting GRP78 (Ad-shGRP78) was constructed and transfected into HepG2 cells. RT-PCR assay was used to determine RNA interference efficiency. Effects of knockdown of GRP78 on adenosine-induced cell viabilities, cell-cycle distribution and apoptosis, as well as relative protein expressions were determined by flow cytometry and/or Western blot analysis. The intracellular Ca2+ concentration was detected by laser scanning confocal microscope. Mitochondrial membrane potential (ΔΨm) was measured by a fluorospectrophotometer. The results revealed that GRP78 mRNA was significantly downregulated by Ad-shGRP78 transfection. Knockdown of GRP78 enhanced HepG2 cell sensitivity to adenosine by modulating G0/G1 arrest and stimulating Bax, Bak, m-calpain, caspase-4 and CHOP protein levels. Knockdown of GRP78 worsened cytosolic Ca2+ overload and ΔΨm loss. Knockdown of caspase-4 by shRNA decreased caspase-3 mRNA expression and cell apoptosis. These findings indicate that GRP 78 plays a protective role in ER stress-induced apoptosis and show that the combination of chemotherapy drug and RNA interference adenoviruses provides a new treatment strategy against malignant tumors.

show abstract

Section: Methodsmentioning

confidence: 99%

Enhanced Antitumor Effects of Adenoviral-Mediated siRNA against GRP78 Gene on Adenosine-Induced Apoptosis in Human Hepatoma HepG2 Cells

Guo

Zhang

et al. 2014

IJMS

View full text Add to dashboard Cite

show abstract

“…Maternal serum levels of TRP fluctuate quite considerably, with the activity of TDO and IDO being tightly regulated both during and after pregnancy ( 10 ) . It has been established that IDO is necessary for the maintenance of pregnancy as it protects the fetus from T-cell-driven local inflammatory responses ( 8 , 10 ) . A study by Schröcksnadel et al ( 10 ) identified that maternal serum TRP levels progressively decreased during pregnancy via immune activation-induced IDO breakdown.…”

mentioning

confidence: 99%

Tryptophan metabolic profile in term and preterm breast milk: implications for health

et al. 2018

View full text Add to dashboard Cite

Breast milk is the only source of the essential amino acid tryptophan (TRP) in breast-fed infants. Low levels of TRP could have implications for infant neurodevelopment. The objectives of the present study were to compare the relationship of TRP and its neuroactive pathway metabolites kynurenine (Kyn) and kynurenic acid (KynA) in preterm and term expressed breast milk (EBM) in the first 14 d following birth, and the relationship of TRP metabolism to maternal stress and immune status. A total of twenty-four mothers were recruited from Cork University Maternity Hospital: twelve term (>38 weeks) and twelve preterm (<35 weeks). EBM samples were collected on days 7 and 14. Free TRP, Kyn and KynA were measured using HPLC, total TRP using MS, cytokines using the Meso Scale Discovery (MSD) assay system, and cortisol using a cortisol ELISA kit. Although total TRP was higher in preterm EBM in comparison with term EBM (P < 0·05), free TRP levels were lower (P < 0·05). Kyn, KynA and the Kyn:TRP ratio increased significantly in term EBM from day 7 to day 14 (P < 0·05), but not in preterm EBM. TNF-α, IL-6 and IL-8 were higher in day 7 preterm and term EBM in comparison with day 14. There were no significant differences between term and preterm EBM cortisol levels. Increased availability of total TRP, lower levels of free TRP and alterations in the temporal dynamics of TRP metabolism in preterm compared with term EBM, coupled with higher EBM inflammatory markers on day 7, may have implications for the neurological development of exclusively breast-fed preterm infants.

show abstract

“…Toxic effects of tryptophan metabolites are responsible for inhibition of T cell proliferation and Tregs, and it has been suggested that IdO may be associated with the T helper (Th)1/Th2 cell balance (6,12,13). Both direct and indirect analyses have reported that IdO is associated with human maternal fetal interface and the immune system (14,15).…”

Section: Estrogen Induces Ido Expression Via Tgf-β In Chorionic Villi and Decidua During Early Stages Of Pregnancymentioning

confidence: 99%

Estrogen induces IDO expression via TGF‑β in chorionic villi and decidua during early stages of pregnancy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Indoleamine 2,3-dioxygenase (IdO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternal-fetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17β-estradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor β (TGF-β) and IdO in chorionic villi and decidua tissues. Both TGF-β and IdO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17β-estradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IdO expression increased in a dose-dependent manner in tissue samples cultured in medium containing TGF-β. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IdO by TGF-β, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.

show abstract

Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule

Cited by 9 publications

References 38 publications

Enhanced Antitumor Effects of Adenoviral-Mediated siRNA against GRP78 Gene on Adenosine-Induced Apoptosis in Human Hepatoma HepG2 Cells

Enhanced Antitumor Effects of Adenoviral-Mediated siRNA against GRP78 Gene on Adenosine-Induced Apoptosis in Human Hepatoma HepG2 Cells

Tryptophan metabolic profile in term and preterm breast milk: implications for health

Estrogen induces IDO expression via TGF‑β in chorionic villi and decidua during early stages of pregnancy

Contact Info

Product

Resources

About