Tryptophan metabolite analog, N-(3,4-dimethoxycinnamonyl) anthranilic acid, ameliorates acute graft-versus-host disease through regulating T cell proliferation and polarization

Xu, Jingjing; Wei, Jia; Huang, Min; Zhu, Xianmin; Guan, Jing; Yin, Jin; Xiao, Yi; Zhang, Yicheng

doi:10.1016/j.intimp.2013.08.004

Cited by 10 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 50 IDO activation is suggested to ameliorate GvHD severity and mortality. 56 – 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: 98%

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation

et al. 2017

View full text Add to dashboard Cite

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 CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (tumor necrosis factor α, interferon-γ, interleukin 1 α [IL-1α], 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 cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal impairment.

show abstract

Section: Discussionmentioning

confidence: 98%

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…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: 96%

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

“…As reviewed by Murakami et al 11 , the immunosuppressive effect of IDO results from inhibited T cell proliferation by local depletion of trp, the apoptotic properties of trp metabolites such as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) on T cells, and the ability of IDO to activate mature regulatory T cells (Tregs) and to convert naive T cells to Tregs. In animal models of GVHD, IDO activation is suggested to ameliorate disease severity and reduce mortality 17–19 . In GVHD in humans, kyn urine levels as a marker of IDO activity correlate with disease severity.…”

Section: Discussionmentioning

confidence: 99%

Vascular Alterations in a Murine Model of Acute Graft-Versus-Host Disease Are Associated with Decreased Serum Levels of Adiponectin and an Increased Activity and Vascular Expression of Indoleamine 2,3-Dioxygenase

et al. 2016

View full text Add to dashboard Cite

Graft-versus-host disease (GVHD) is the limiting complication after bone marrow transplantation (BMT), and its pathophysiology seems to be highly influenced by vascular factors. Our study aimed at elucidating possible mechanisms involved in vascular GVHD. For this purpose, we used a fully MHC-mismatched model of BALB/c mice conditioned according to two different intensity protocols with total body irradiation and transplantation of allogeneic (C57BL/6) or syngeneic bone marrow cells and splenocytes. Mesenteric resistance arteries were studied in a pressurized myograph. We also quantified the expression of indoleamine 2,3-dioxygenase (IDO), endothelial (eNOS), and inducible NO synthase (iNOS), as well as several pro-and anti-inflammatory cytokines. We measured the serum levels of tryptophan (trp) and kynurenine (kyn), the kyn/trp ratio (KTR) as a marker of IDO activity, and adiponectin (APN). The myographic study showed a correlation of GVHD severity after allogeneic BMT with functional vessel alterations that started with increased vessel stress and ended in eccentric vessel remodeling, increased vessel strain, and endothelial dysfunction. These alterations were accompanied by increasing IDO activity and decreasing APN levels in the serum of allogeneic animals. The mRNA expression showed significantly elevated IDO, decreased eNOS, and elevation of most studied pro-and anti-inflammatory cytokines. Our study provides further data supporting the importance of vessel alterations in GVHD and is the first to show an association of vascular GVHD with hypoadiponectinemia and an increased activity and vascular expression of IDO. Whether there is also a causative involvement of these two factors in the development of GVHD needs to be further investigated.

show abstract

Tryptophan metabolite analog, N-(3,4-dimethoxycinnamonyl) anthranilic acid, ameliorates acute graft-versus-host disease through regulating T cell proliferation and polarization

Cited by 10 publications

References 31 publications

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation

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

Vascular Alterations in a Murine Model of Acute Graft-Versus-Host Disease Are Associated with Decreased Serum Levels of Adiponectin and an Increased Activity and Vascular Expression of Indoleamine 2,3-Dioxygenase

Contact Info

Product

Resources

About