Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells

Mohib, Kanishka; Guan, Qiunong; Diao, Hong; Du, Caigan; Jevnikar, Anthony M.

doi:10.1152/ajprenal.00044.2007

Cited by 49 publications

(53 citation statements)

References 41 publications

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“…Renal IRI causes severe tissue injury and various forms of cell death [4,5,6,7,8] including apoptosis, necrosis, autophagy, and other nonclassical forms of cell death [42]. During necrotic cell death, cells invariably lose membrane integrity and eventually lyse, resulting in the release of intracellular contents and various DAMP such as HMGB1.…”

Section: Resultsmentioning

confidence: 99%

“…The TEC line NG1.1 was developed from proximal TEC of C57BL/6J mice by SV40 transformation as previously described [4]. NK cells were purified from C57BL/6J mouse spleens using anti-CD49a MACS bead selection (Miltenyi Biotec) and were grown in the presence of IL-2 (1,000 IU/ml) in RPMI-1640.…”

Section: Methodsmentioning

confidence: 99%

“…The initial ischemic insult induces widespread death of kidney parenchymal cells and in particular tubular epithelial cells (TEC) [4,5,6,7,8], which results in organ dysfunction and the release of damage-associated molecular pattern (DAMP) proteins into the extracellular space [9,10,11,12,13]. High-mobility group box-1 (HMGB1) and other DAMP moieties may further contribute to proinflammatory injury [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Glycyrrhizic Acid Ameliorates HMGB1-Mediated Cell Death and Inflammation after Renal Ischemia Reperfusion Injury

et al. 2014

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Background: Renal ischemia reperfusion injury (IRI) leads to acute kidney injury (AKI) and the death of tubular epithelial cells (TEC). The release of high-mobility group box-1 (HMGB1) and other damage-associated molecular pattern moieties from dying cells may promote organ dysfunction and inflammation by effects on TEC. Glycyrrhizic acid (GZA) is a functional inhibitor of HMGB1, but its ability to attenuate the HMGB1-mediated injury of TEC has not been tested. Methods/Results: In vitro, hypoxia and cytokine treatment killed TEC and resulted in the progressive release of HMGB1 into the supernatant. GZA reduced the hypoxia-induced TEC death as measured by annexin-V and propidium iodide. Hypoxia increased the expression of MCP-1 and CXCL1 in TEC, which was reduced by GZA in a dose-dependent manner. Similarly, the HMGB1 activation of effector NK cells was inhibited by GZA. To test the effect of HMGB1 neutralization by GZA in vivo, mice were subjected to renal IRI. HMGB1 protein expression increased progressively in kidneys from 4 to 24 h after ischemia and was detected in tubular cells by 4 h using immunohistochemistry. GZA preserved renal function after IRI and reduced tubular necrosis and neutrophil infiltration by histological analyses and ethidium homodimer staining. Conclusions: Importantly, these data demonstrate for the first time that AKI following hypoxia and renal IRI may be promoted by HMGB1 release, which can reduce the survival of TEC and augment inflammation. Inhibition of the interaction of HMGB1 with TEC through GZA may represent a therapeutic strategy for the attenuation of renal injury following IRI and transplantation.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glycyrrhizic Acid Ameliorates HMGB1-Mediated Cell Death and Inflammation after Renal Ischemia Reperfusion Injury

et al. 2014

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“…Given that isc DCs appear to migrate more rapidly to recipients LNs, it follows that a more robust recipient T cell response would occur and that graft survival would be accordingly more compromised. Our observation that isc DCs undergo significantly more apoptosis than ctrl DCs provide a further mechanism by which isc grafts display greater immunogenicity, as apoptosis and necrosis of donor cells have been implicated in the established increased immunogenicity of isc allografts (77)(78)(79)(80)(81)(82). DCs have also been specifically implicated in acquiring Ag from apoptotic cells to stimulate class Irestricted cytotoxic T cells (83,84).…”

Section: Discussionmentioning

confidence: 79%

Ischemic Injury Enhances Dendritic Cell Immunogenicity via TLR4 and NF-κB Activation

Jurewicz

Takakura

Augello

et al. 2010

The Journal of Immunology

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Ischemic (isc) injury during the course of transplantation enhances the immunogenicity of allografts and thus results in poorer graft outcome. Given the central role of dendritic cells (DCs) in mounting alloimmune responses, activation of donor DCs by ischemia may have a primary function in the increased immunogenicity of isc allografts. In this study, we sought to investigate the effect of ischemia on DC activity in vitro. Following induction of ischemia, bone marrow-derived DCs were shown to augment allogeneic T cell proliferation as well as the IFN-γ response. Isc DCs produced greater levels of IL-6, and isc insult was concurrent with NF-κB activation. TLR4 ligation was also shown to occur in isc DCs, most likely in response to the endogenous ligand heat shock protein 70, which was found to be elevated in DCs following isc injury, and lack of TLR4 abrogated the observed effects of isc DCs. As compared with control DCs, isc DCs injected into the footpads of mice demonstrated enhanced migration, which was concomitant with increased recipient T cell activity. Moreover, isc DCs underwent a greater degree of apoptosis in the lymph nodes of injected mice, which may further demonstrate enhanced immunogenicity of isc DCs. We thus show that isc injury of DCs enhances DC function, augments the allogeneic T cell response, and occurs via ligation of TLR4, followed by activation of NF-κB. These data may serve to identify novel therapeutic targets to attenuate graft immunogenicity following ischemia.

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“…These findings are of particular interest given animal and cellular studies that implicate tryptophan metabolism through the kynurenine pathway as a mediator of renal injury (4,5), and demonstrate functional roles to kynurenine and kynurenic acid in vascular tone and inflammation (6,7). Other risk markers identified in the FHS included citrulline (OR per 11.48 SD, 1.38; P,0.001; 95% CI, 1.19 to 1.83; [3]) and choline (OR per 11 SD, 1.46; P,0.001; 95% CI, 1.17 to 1.82; [3]).…”

mentioning

confidence: 99%

Metabolite Markers of Incident CKD Risk

Rhee

Feldman

2014

Clinical Journal of the American Society of Nephrology

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The systematic analysis of metabolites (e.g., sugars, amino acids, organic acids, lipids, etc.) in biologic specimens is referred to as metabolomics or metabolite profiling. Downstream of transcriptional and translational processes, metabolite profiles can provide proximal reports of the body's metabolic state and are also influenced by environmental factors such as diet, medications, and the gut microbiome (1). Increasing interest has been directed toward the metabolomic characterization of kidney disease because of its association with various metabolic disorders, because of the broad effect that renal dysfunction has on circulating metabolites, and because circulating metabolites may themselves participate in pathways relevant to disease pathogenesis and progression.The value of metabolite profiling in clinical research can be enhanced when applied to large, richly phenotyped cohorts. In addition to increasing statistical power, this approach permits assessment of the association of baseline metabolite levels with longitudinal renal outcomes. For example, Goek et al. examined longitudinal associations of baseline levels of 140 metabolites with change in eGFR and incident CKD over 7 years in 1017 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 (KORA) study (2). Similarly, Rhee et al. examined the longitudinal association of baseline levels of 217 metabolites with incident CKD over 8 years in 1434 participants of the Framingham Heart Study (FHS) (3). In both studies, participants were predominantly of European ancestry and all had an eGFR$60 ml/min per 1.73 m 2 at baseline. Incident CKD was defined as an eGFR,60 ml/min per 1.73 m 2 at follow-up, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease equations, respectively. A total of 106 individuals in the KORA study and 123 individuals in the FHS developed new-onset CKD. Interestingly, both studies identified markers of tryptophan metabolism as associated with the occurrence of CKD. In the KORA study, the strongest association was with the kynurenine/tryptophan ratio, with an odds ratio (OR) of 1.36 per SD (P50.003; 95% confidence interval [95% CI], 1.11 to 1.66; [2]) after adjusting for eGFR and other CKD risk factors. The FHS, which did not examine metabolite ratios, also highlighted that kynurenine (OR per 11 SD, 1.49; P,0.001; 95% CI, 1.22 to 1.83; [3]) as well as its downstream metabolite kynurenic acid (OR per 11 SD, 1.53; P,0.001; 95% CI, 1.25 to 1.88; [3]) were related to the risk of future CKD.These findings are of particular interest given animal and cellular studies that implicate tryptophan metabolism through the kynurenine pathway as a mediator of renal injury (4,5), and demonstrate functional roles to kynurenine and kynurenic acid in vascular tone and inflammation (6,7). Other risk markers identified in the FHS included citrulline (OR per 11.48 SD, 1.38; P,0.001; 95% CI, 1.19 to 1.83; [3]) and choline (OR per 11 SD, 1.46; P,0.001; 95% CI, 1.17 to 1.82; [3])....

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Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells

Cited by 49 publications

References 41 publications

Glycyrrhizic Acid Ameliorates HMGB1-Mediated Cell Death and Inflammation after Renal Ischemia Reperfusion Injury

Glycyrrhizic Acid Ameliorates HMGB1-Mediated Cell Death and Inflammation after Renal Ischemia Reperfusion Injury

Ischemic Injury Enhances Dendritic Cell Immunogenicity via TLR4 and NF-κB Activation

Metabolite Markers of Incident CKD Risk

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