3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3-dioxygenase pathway, suppresses inducible nitric oxide synthase expression by enhancing heme oxygenase-1 expression

Oh, Gi‐Su; Pae, Hyun‐Ock; Choi, Byung-Min; Chae, Soo-Cheon; Lee, Ho-Sub; Ryu, Do-Gon; Chung, Hun‐Taeg

doi:10.1016/j.bbrc.2004.06.061

Cited by 87 publications

(67 citation statements)

References 27 publications

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“…Indeed, the ability of 3-HAA to induce HO-1 has been previously shown in mouse macrophage cell lines. 60 In our study, microglia showed significant differences from astrocytes in the expression of HO-1 because microglial HO-1 was suppressed by TLR ligands but enhanced by the antiinflammatory cytokine IL-10. The findings in microglia are similar to those reported in macrophages 44 -46 and support the notion that HO-1 may be a marker of "alternatively activated" (M2) macrophage phenotype.…”

Section: Discussionmentioning

confidence: 51%

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

Krause

Suh

Tarassishin

et al. 2011

The American Journal of Pathology

143

104

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Tryptophan metabolism by the kynurenine pathway (KP) is important to the pathogenesis of inflammatory, infectious, and degenerative diseases. The 3-hydroxykynurenine (3-HK) branch of the KP is activated in macrophages and microglia, leading to the generation of 3-HK, 3-hydroxyanthranilic acid (3-HAA), and quinolinic acid, which are considered neurotoxic owing to their free radical-generating and N-methyl-D-aspartic acid receptor agonist activities. We investigated the role of 3-HAA in inflammatory and antioxidant gene expression and neurotoxicity in primary human fetal central nervous system cultures treated with cytokines (IL-1 with or without interferon-␥) or with Toll-like receptor ligands mimicking the proinflammatory central nervous system environment. Results were analyzed by microarray, Western blot, immunostain, enzyme-linked immunosorbent assay, and neurotoxicity assays. 3-HAA suppressed glial cytokine and chemokine expression and reduced cytokine-induced neuronal death. 3-HK also suppressed cytokineinduced neuronal death. Unexpectedly, 3-HAA was highly effective in inducing in astrocytes the expression of hemeoxygenase-1 (HO-1), an antioxidant enzyme with anti-inflammatory and cytoprotective properties. Indoleamine-2,3-dioxygenase (IDO) is an interferon (IFN)-␥-inducible, rate-limiting enzyme in the kynurenine pathway (KP) of tryptophan metabolism generating various downstream metabolites collectively termed "kynurenines" 1 ( Figure 1). This process is compartmentalized due to cell-specific expression of the KP enzymes. For example, kynurenine monooxygenase (KMO) is expressed in macrophages and microglia, 2-4 whereas kynurenine aminotransferase II (KAT II) is present in astrocytes.5 A well-appreciated biological activity of IDO is T-cell suppression. IDO expressed in antigen-presenting cells (dendritic cells, macrophages, and microglia) can

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Section: Discussionmentioning

confidence: 51%

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

Krause

Suh

Tarassishin

et al. 2011

The American Journal of Pathology

143

104

View full text Add to dashboard Cite

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“…Although preliminary at this time, a recent publication by Oh et al (55) demonstrated that the IDO metabolite HA may influence the expression of HO-1. The authors showed that HA was capable of blocking inducible NO synthase (iNOS) expression and NO production by up-regulating HO-1 expression.…”

Section: Another Potential Gap: a Role For Ido In Modifying Treg Funcmentioning

confidence: 83%

An Integral Role for Heme Oxygenase-1 and Carbon Monoxide in Maintaining Peripheral Tolerance by CD4+CD25+ Regulatory T Cells

Brusko

Wasserfall

Agarwal

et al. 2005

The Journal of Immunology

115

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Over the past decade, a great deal of interest and attention has been directed toward a population of regulatory T cells (Treg) coexpressing the markers CD4 and CD25. The hallmark phenotype of this cell population resides in its ability to dominantly maintain peripheral tolerance and avert autoimmunity. Despite robust research interest in Treg, their mechanism of action and interaction with other cell populations providing immune regulation remains unclear. In this study, we present a model for Treg activity that implicates carbon monoxide, a by-product of heme oxygenase-1 activity, as an important and underappreciated facet in the suppressive capacity of Treg. Our hypothesis is based on recent evidence supporting a role for heme oxygenase-1 in regulating immune reactivity and posit carbon monoxide to function as a suppressive molecule. Potential roles for indoleamine 2,3-dioxygenase, costimulatory molecules, and cytokines in tolerance induction are also presented. This model, if validated, could act as a catalyst for new investigations into Treg function and ultimately result in novel methods to modulate Treg biology toward therapeutic applications.

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“…This finding was the same as previously reported. 21 Furthermore, after stimulation with IFNγ and LPS for 24 h, RAW264.7 cells were treated with FAPτ, FAPτ-MT or 1-MT for another 24 h. The tryptophan level in the cells treated with FAPτ-MT increased significantly compared to the cells treated with FAPτ alone (p < 0.01). However, the kynurenine significantly decreased (p < 0.01) (Fig.…”

Section: Inhibition Of Ido Activity In Macrophages Bymentioning

confidence: 95%

A new tumor vaccine: FAPτ-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells

Yi¹,

Zhang²,

Zeng³

et al. 2011

Cancer Biology & Therapy

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3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3-dioxygenase pathway, suppresses inducible nitric oxide synthase expression by enhancing heme oxygenase-1 expression

Cited by 87 publications

References 27 publications

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

An Integral Role for Heme Oxygenase-1 and Carbon Monoxide in Maintaining Peripheral Tolerance by CD4+CD25+ Regulatory T Cells

A new tumor vaccine: FAPτ-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells

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