Tryptophan metabolite 3-hydroxyanthranilic acid selectively induces activated T cell death via intracellular GSH depletion

Lee, Sun-Mi; Lee, Young-Suk; Choi, Jae-Hyeog; Park, Sae-Gwang; Choi, Il‐Whan; Joo, Young-Don; Lee, Won-Sik; Lee, Jeong-Nyeo; Choi, Inhak; Seo, Su‐Kil

doi:10.1016/j.imlet.2010.05.008

Cited by 68 publications

(46 citation statements)

References 38 publications

(42 reference statements)

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“…Underlined metabolites were measured by the LC-MS/MS method described amide (NAm) and nicotinic acid (NA) [6]. Most catabolites are biologically active and involved in the pathogenesis of many disease processes [7][8][9][10][11][12]. Furthermore, the interrelationship between metabolic pathways is of profound pharmacological and physiological importance as changes in one pathway might have secondary effects on the others [1].…”

Section: Introductionmentioning

confidence: 99%

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

et al. 2011

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A sensitive, selective, and comprehensive method for the quantitative determination of tryptophan and 18 of its key metabolites in serum, urine, and cell culture supernatants was developed. The analytes were separated on a C18 silica column by reversed-phase liquid chromatography and detected by electrospray ionization tandem mass spectrometry in positive ion multiple reaction monitoring (MRM) mode, except for indoxyl sulfate which was measured in negative ion MRM mode in a separate run. The limits of detection and lower limits of quantification were in the range of 0.1-50 and 0.5-100 nM, respectively. Fully 13 C isotope-labeled and deuterated internal standards were used to achieve accurate quantification. The applicability of the method to analyze serum, urine, and cell culture supernatants was demonstrated by recovery experiments and the evaluation of matrix effects. Precision for the analysis of serum, urine, and cell culture supernatants ranged between 1.3% and 16.0%, 1.5% and 13.5%, and 1.0% and 17.4%, respectively. The method was applied to analyze changes in tryptophan metabolism in cell culture supernatants from IFN-γ-treated monocytes and immature or mature dendritic cells.

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Section: Introductionmentioning

confidence: 99%

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

et al. 2011

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“…50 IDO activation is suggested to ameliorate GvHD severity and mortality. [56][57][58] High expression of IDO in intestinal mucosal mononuclear cells and low expression in endothelial cells were associated with favorable outcome in intestinal GvHD. 59 In our study, we could find higher IDO expression levels after allogeneic BMT in both HIP and LIP animals.…”

Section: Discussionmentioning

confidence: 99%

Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

et al. 2017

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Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets of graft-versus-host disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols. Syngeneically transplanted and untreated animals served as controls. Four weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T cells consisted of CD4þ, CD8þ, and FoxP3þ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (tumor necrosis factor a, interferon-g, interleukin 1 a [IL-1a], IL-2, IL-6, and IL-10), and adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cellmediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal impairment.

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“…Two possible mechanisms of apoptosis are proposed: 1) depletion of tryptophan (de la Maza and Peterson, 1988;Ozaki et al, 1988;Lee et al, 2002;Platten et al, 2012) and 2) production of toxic tryptophan metabolites in the kynurenine pathway, such as kynurenines and 3-hydroxyanthranilic (3-HAA) (Morita et al, 2001;Fallarino et al, 2003;Mailankot et al, 2009;Lee et al, 2010;Mailankot and Nagaraj, 2010;Song et al, 2011;Hou et al, 2014). In this study, we demonstrated that the addition of either the IDO inhibitor 1-MT or L-tryptophan could decrease IFN-γ-induced reduction of cell viability ( Figure 5A) and apoptosis ( Figure 5B-E).…”

Section: Discussionmentioning

confidence: 99%

Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

Chung

Tan

Chan

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Tryptophan metabolite 3-hydroxyanthranilic acid selectively induces activated T cell death via intracellular GSH depletion

Cited by 68 publications

References 38 publications

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

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