Inhibition of indoleamine 2,3-dioxygenase activity by fatty acids and prostaglandins: A structure function analysis

Costabile, Maurizio; Bassal, Nesrine Kamal; Gerber, Jacobus P.; Hughes, B P

doi:10.1016/j.plefa.2017.06.010

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Some studies demonstrated that EPA could inhibit IDO expression in tumor cells, 15 while EPA‐derived metabolite resolvin E1 can induce several biological responses, including inhibition of dendritic cell migration and leukocyte infiltration, modulation of IDO synthesis in dendritic cells, inhibition of T cell activation, and modulation of effector T cell death 16 . Furthermore, AA, DHA and dihomo‐γ‐linolenic acid are potent inhibitors of IDO in human acute monocytic leukemic THP‐1 cells and primary human monocytes 17,41 . In addition, some reports revealed that an increase in activity of IDO can promote fatty acid oxidation 42 .…”

Section: Discussionmentioning

confidence: 99%

“…16 Furthermore, AA, DHA and dihomo-γ-linolenic acid are potent inhibitors of IDO in human acute monocytic leukemic THP-1 cells and primary human monocytes. 17,41 In addition, some reports revealed that an increase in activity of IDO can promote fatty acid oxidation. 42 Recently, Ele and collaborators found that IDO can promote the downregulation of essential enzymes related to fatty acid synthesis in CD4 + T cells, inhibit fatty acid synthesis, and CD4 + T cell proliferation and differentiation.…”

Section: Correlation Analysis Between Tryptophan-kynurenine Pathway A...mentioning

confidence: 99%

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Correlation between immune‐related Tryptophan‐Kynurenine pathway and severity of severe pneumonia and inflammation‐related polyunsaturated fatty acids

Guo,

Xue,

Zhang

et al. 2023

Immunity Inflam & Disease

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BackgroundImmune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia.ObjectiveThis study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan‐Kynurenine pathway and the severity of severe pneumonia, as well as N‐3/N‐6 polyunsaturated fatty acids (PUFAs).MethodsIn this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups.ResultsMetabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α‐linolenic acid (linolenic acid, α‐LNA), arachidonic acid (ARA), Dihomo‐γ‐linolenic acid (DGLA), and 13(s)‐hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)‐hydroxyeicosatetraenoic acid (HETE), 11(S)‐HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)‐hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α‐LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)‐HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α‐LNA, DHA, and DPA.ConclusionThis study revealed that during severe pneumonia, the Tryptophan‐Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan‐Kynurenine pathway was negatively correlated with N‐3/N‐6 PUFAs.

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Section: Discussionmentioning

confidence: 99%

Section: Correlation Analysis Between Tryptophan-kynurenine Pathway A...mentioning

confidence: 99%

Correlation between immune‐related Tryptophan‐Kynurenine pathway and severity of severe pneumonia and inflammation‐related polyunsaturated fatty acids

Guo,

Xue,

Zhang

et al. 2023

Immunity Inflam & Disease

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show abstract

“…Consistent with this, the overexpression of COX-2 described in mammary tumor cells is associated with increased IDO1 and kynurenine levels [200] in co-cultured fibroblasts. Surprisingly, arachidonic acid itself interferes with the IFNγ and STAT3 induction of IDO1, and compounds are being developed to reproduce this phenomenon by mimicking the inhibitory effect of arachidonate on IDO1 expression [201].…”

Section: Cox and Oxidative Stressmentioning

confidence: 99%

Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

Stone

Williams

2023

Cancers

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The mechanisms underlying a relationship between inflammation and cancer are unclear, but much emphasis has been placed on the role of tryptophan metabolism to kynurenine and downstream metabolites, as these make a substantial contribution to the regulation of immune tolerance and susceptibility to cancer. The proposed link is supported by the induction of tryptophan metabolism by indoleamine-2,3-dioxygenase (IDO) or tryptophan-2,3-dioxygenase (TDO), in response to injury, infection or stress. This review will summarize the kynurenine pathway and will then focus on the bi-directional interactions with other transduction pathways and cancer-related factors. The kynurenine pathway can interact with and modify activity in many other transduction systems, potentially generating an extended web of effects other than the direct effects of kynurenine and its metabolites. Conversely, the pharmacological targeting of those other systems could greatly enhance the efficacy of changes in the kynurenine pathway. Indeed, manipulating those interacting pathways could affect inflammatory status and tumor development indirectly via the kynurenine pathway, while pharmacological modulation of the kynurenine pathway could indirectly influence anti-cancer protection. While current efforts are progressing to account for the failure of selective IDO1 inhibitors to inhibit tumor growth and to devise means of circumventing the issue, it is clear that there are wider factors involving the relationship between kynurenines and cancer that merit detailed consideration as alternative drug targets.

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“…Indoleamine 2,3-dioxygenase-1 (IDO-1) speed up the L-tryptophan metabolism, which produces numerous immunosuppressive metabolites, like kynurenine. Thus it causes immunosuppression, T cell negative regulation & contribute in tumor management [13]. Indoleamine 2,3-dioxygenase (IDO), enhances nitric oxide synthase liable for breakdown of tryptophan and arginine [14].…”

Section: Nsaidsmentioning

confidence: 99%

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

Dawood

Bano²,

Sundus

et al. 2022

JPRI

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Objective: To study the effects of anti-inflammatory medication on Indoleamine 2,3 dioxygenase activity. Research Design: This was an investigational study. Methodology: Eighteen fully grown albino rats separated into control and two treated sets, both treated sets were given indomethacin (50mg/1000g) orally. For acute treatment first treated set was sacrificed after 3.5 hrs & for chronic treatment second set was sacrificed after 3 days. However, control set animals were given an equivalent amount of vehicle. Results: Outcomes shows that serum Indoleamine 2,3 dioxygenase (IDO) enzyme activity was suppressed after acute treatment while serum IDO activity were increased after chronic treatment however no significant effect was seen on brain IDO. Conclusion: It is concluded that indomethacin has not shown any significant effect on brain IDO. But inhibits serum IDO activity.

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Inhibition of indoleamine 2,3-dioxygenase activity by fatty acids and prostaglandins: A structure function analysis

Cited by 7 publications

References 28 publications

Correlation between immune‐related Tryptophan‐Kynurenine pathway and severity of severe pneumonia and inflammation‐related polyunsaturated fatty acids

Correlation between immune‐related Tryptophan‐Kynurenine pathway and severity of severe pneumonia and inflammation‐related polyunsaturated fatty acids

Interactions of IDO and the Kynurenine Pathway with Cell Transduction Systems and Metabolism at the Inflammation–Cancer Interface

Effects of Anti-inflammatory Medication on Indoleamine 2,3 Dioxygenase Activity

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