Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways

Odemuyiwa, Solomon O.; Ebeling, Cory; Duta, V.; Abel, M; Puttagunta, Lakshmi; Cravetchi, Olga Vladimir; Majaesic, C.; Vliagoftis, H.; Moqbel, Redwan

doi:10.1111/j.1398-9995.2008.01809.x

Cited by 19 publications

(16 citation statements)

References 15 publications

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“…Thus, intratracheal instillation of 3-HAA ameliorates experimental asthma in OVA-challenged mice by impairing the functionality of, and inducing apoptosis in, Th2 cells via inhibiting NF-κB signalling within these cells [236]. In a murine model of mucosal tolerance, although IDO1 inhibition with 1-MT attenuated OVA-induced tolerance upon OVA-sensitisation and rechallenge, treatment with a mixture of Kyn and 3-HAA restored tolerance in 1-MT-treated mice [321]. Similarly, administration of Kyn, 3-HK or xanthurenic acid reduced lung eosinophil and Th2 cytokine levels in allergic mice receiving suboptimal allergen immunotherapy [320].…”

Section: Transplantation the Ultimate Goal In Organ Transplantationmentioning

confidence: 81%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

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IDO1 (indoleamine 2,3-dioxygenase 1) is a member of a unique class of mammalian haem dioxygenases that catalyse the oxidative catabolism of the least-abundant essential amino acid, L-Trp (L-tryptophan), along the kynurenine pathway. Significant increases in knowledge have been recently gained with respect to understanding the fundamental biochemistry of IDO1 including its catalytic reaction mechanism, the scope of enzyme reactions it catalyses, the biochemical mechanisms controlling IDO1 expression and enzyme activity, and the discovery of enzyme inhibitors. Major advances in understanding the roles of IDO1 in physiology and disease have also been realised. IDO1 is recognised as a prominent immune regulatory enzyme capable of modulating immune cell activation status and phenotype via several molecular mechanisms including enzyme-dependent deprivation of L-Trp and its conversion into the aryl hydrocarbon receptor ligand kynurenine and other bioactive kynurenine pathway metabolites, or non-enzymatic cell signalling actions involving tyrosine phosphorylation of IDO1. Through these different modes of biochemical signalling, IDO1 regulates certain physiological functions (e.g. pregnancy) and modulates the pathogenesis and severity of diverse conditions including chronic inflammation, infectious disease, allergic and autoimmune disorders, transplantation, neuropathology and cancer. In the present review, we detail the current understanding of IDO1's catalytic actions and the biochemical mechanisms regulating IDO1 expression and activity. We also discuss the biological functions of IDO1 with a focus on the enzyme's immune-modulatory function, its medical implications in diverse pathological settings and its utility as a therapeutic target.

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Section: Transplantation the Ultimate Goal In Organ Transplantationmentioning

confidence: 81%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

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“…1a), which has previously demonstrated that intraperitoneal (i.p.) injection of Alum/OVA cannot sensitize mice to allergic airway disease that have already been exposed to inhaled OVA in the absence of an adjuvant (20). In our hands, tolerized mice that underwent a subsequent sensitization regimen via i.p.…”

Section: Resultsmentioning

confidence: 99%

“…Splenocytes were isolated using Lymphocyte Separation Media (MP Biomedicals, Solon, OH) following mechanical disruption as previously described (20). 4 × 10 6 cells/ml were cultured in RPMI-1640 supplemented with 10% FBS (Cell Generation, Fort Collins, CO), penicillin/streptomycin, L-glutamine, folic acid, and 2-ME and treated with 100 μg/ml OVA.…”

Section: Methodsmentioning

confidence: 99%

Airway epithelial NF‐κB activation promotes the ability to overcome inhalational antigen tolerance

Ather

Foley

Suratt

et al. 2015

Clin Experimental Allergy

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Background Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development of asthma. Objectives We examined in vivo whether pre-existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF-κB in conducting airway epithelial cells, and used a combination of in vivo and in vitro approaches to examine the mechanisms involved. Methods Wildtype and transgenic mice capable of expressing constitutively active IκB kinase β (CAIKKβ) in airway epithelium were tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA on day 30 in an attempt to overcome inhalational tolerance. Results Following ovalbumin challenge on days 40-42, CAIKKβ mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyperresponsiveness. Increases in the CD103+ and CD11bHI lung dendritic cell populations were present in CAIKKβ mice on day 31. Bronchoalveolar lavage from mice expressing CAIKKβ mice induced CD4+ T cells to secrete TH2 and TH17 cytokines, an effect that required IL-4 and IL-1 signaling, respectively. CAIKKβ mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated mRNA expression of the TH2-polarizing cytokine IL-4. Finally, airway epithelial NF-kB activation induced allergic sensitization in CAIKKβ mice on Dox that required IL-4 and IL-1-signaling in vivo. Conclusions Our studies demonstrate that soluble mediators generated in response to airway epithelial NF-κB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL-1 and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD4+ T cells.

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“…In one study, the mouse model used involved intranasal inoculation of lipopolysaccharide-free ovalbumin with subsequent tests for tolerance by intraperitoneal sensitization and intranasal re-challenge [57]. In the same model, another study reported that 1MT could partly reverse the suppressive effects of immunotherapy on airway eosinophilia and Th2 cytokine levels.…”

Section: Ido In Allergic Airway Disease and Asthmamentioning

confidence: 99%

Indoleamine 2,3-dioxygenase as a Modifier of Pathogenic Inflammation in Cancer and other Inflammation-Associated Diseases

Prendergast¹,

Chang²,

Mandik-Nayak³

et al. 2011

CMC

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Chronic inflammation underlies the basis for development and progression of cancers and a variety of other disorders, but what specifically defines its pathogenic nature remains largely undefined. Recent genetic and pharmacological studies in the mouse suggest that the immune modulatory enzyme indoleamine 2,3-dioxygenase (IDO), identified as an important mediator of immune escape in cancer, can also contribute to the development of pathology in the context of chronic inflammatory models of arthritis and allergic airway disease. IDO-deficient mice do not display spontaneous disorders of classical inflammation and small molecule inhibitors of IDO do not elicit generalized inflammatory reactions. Rather, in the context of a classical model of skin cancer that is promoted by chronic inflammation, or in models of inflammation-associated arthritis and allergic airway disease, IDO impairment can alleviate disease severity. Here we offer a survey of preclinical literature suggesting that IDO functions as a modifier of inflammatory states rather than simply as a suppressor of immune function. We propose that IDO induction in a chronically inflamed tissue may shape the inflammatory state to support, or in some cases retard, pathogenesis and disease severity.

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Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways

Abstract: Our data suggest that, in addition to their role in IFN-gamma-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway.

Cited by 19 publications

References 15 publications

Role of indoleamine 2,3-dioxygenase in health and disease

Role of indoleamine 2,3-dioxygenase in health and disease

Airway epithelial NF‐κB activation promotes the ability to overcome inhalational antigen tolerance

Indoleamine 2,3-dioxygenase as a Modifier of Pathogenic Inflammation in Cancer and other Inflammation-Associated Diseases

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