L-Kynurenine and its breakdown products have a variety of biological functions, including vasodilatation during inflammation and modulation of the immune response. Some cancers increase the secretion of L-Kynurenine, which promotes tumour growth, and is also an AHR agonist that activates AHR-induced naive T cell polarisation to an anti-inflammatory Treg phenotype. At physiological concentrations, L-Kynurenine activates AHR signalling in H1L7.5c3 cells after 24 hours of action[1].
Kynurenine/L-犬尿氨酸 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human monocyte-derived macrophages (MDMs)
25 μM
20 hours
To investigate the effect of KYN on NAD+ levels, results showed that KYN supplementation prevented FK866-induced depletion of NAD+.
Nat Immunol. 2019 Jan;20(1):50-63.
K562 human chronic myeloid leukemia cells
50 µM
16 h
To study the effect of LKU on T cell cytotoxicity, it was found that LKU reduced the cytotoxic activity of T cells.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
Primary human CD3-positive T cells
50 µM
16 h
To study the effect of LKU on HIF-1 activity, it was found that VEGF mRNA levels were significantly upregulated in the presence of IDO1 inhibitors.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
Jurkat T cells
50 µM
16 h
To study the effect of LKU on HIF-1 activity, it was found that VEGF mRNA levels were significantly increased in Jurkat T cells.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
WT-3ab Wilms’ tumor cells
50 µM
4 h
To study the effect of LKU on intracellular LKU levels, it was found that LKU levels were significantly increased in WT-3ab cells.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
LN18 human glioblastoma cells
50 µM
4 h
To study the effect of LKU on intracellular LKU levels, it was found that LKU levels were not significantly increased in LN18 cells.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
MCF-7 human breast cancer cells
50 µM
4 h
To study the effect of LKU on HIF-1α nuclear translocation, it was found that LKU downregulated HIF-1α nuclear levels under hypoxic conditions.
Oncoimmunology. 2023 Aug 10;12(1):2244330.
Murine CD4+ T cells
1 mM
3 h
To investigate the effect of D-kynurenine on murine T cell metabolism, found it increased fatty acid β-oxidation leading to fatty acid depletion.
EBioMedicine. 2021 Dec;74:103734.
Human CD4+ T cells
1 mM
3 days
To evaluate the effect of D-kynurenine on T cell proliferation and apoptosis, results showed 1 mM D-kynurenine inhibits T cell proliferation through apoptosis.
EBioMedicine. 2021 Dec;74:103734.
Primary human NK cells
200 μM
48 h
To investigate the effect of L-KYN on primary human NK cell viability, it was found that L-KYN significantly increased the proportion of primary human NK cell death
J Exp Clin Cancer Res. 2023 Mar 1;42(1):52.
NK-92 cells
200 μM
24 or 48 h
To investigate the effect of L-KYN on NK-92 cell viability, it was found that L-KYN significantly increased the proportion of NK-92 cell death
J Exp Clin Cancer Res. 2023 Mar 1;42(1):52.
Arabidopsis thaliana seedlings
0.01 μM -1 mM
3 days
To evaluate the inhibitory effect of Kyn on root growth in Arabidopsis thaliana seedlings. The results showed that Kyn significantly inhibited root growth in a concentration-dependent manner
Plant Cell. 2011 Nov;23(11):3944-60.
conventional dendritic cells (cDCs)
50 μM
24 h
To evaluate the ability of L-Kynurenine to induce IDO1 expression and TGF-β production in LPS-primed cDCs. Results showed that L-Kynurenine significantly enhanced IDO1 expression and TGF-β production, an effect dependent on AhR activation.
Front Immunol. 2020 Mar 11;11:292.
Kynurenine/L-犬尿氨酸 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
B6/Rag1-/- colitis model
Dietary supplementation
300 mg/kg
10 days
To evaluate the protective effect of D-kynurenine on autoimmune colitis, results showed D-kynurenine protected mice from colitis in an AhR-dependent manner.
EBioMedicine. 2021 Dec;74:103734.
HIL-15 NOG mice
Humanized CDX tumor model
Subcutaneous injection
4 μg
Every other day for 14 days
To investigate the effect of L-KYN on NK cells in the tumor microenvironment, it was found that L-KYN significantly reduced the number of NK cells in tumor tissues and increased their death rate
J Exp Clin Cancer Res. 2023 Mar 1;42(1):52.
Mice
Tauopathy mouse model
Intraperitoneal injection
33 mg/10 ml/kg
Single injection, sacrificed after 3 hours
To investigate the effects of Kynurenine on neuroinflammation and neurodegeneration in a tauopathy mouse model. Results showed that Kynurenine levels were elevated in the brains of tauopathy model mice, and Amino LP7 treatment significantly reduced these levels, suppressing neuroinflammation and brain atrophy.
Sci Adv. 2021 Oct 22;7(43):eabd5046
Mice
Cardiac arrest model
Intravenous injection
20 mg/kg
Single dose, observed for 7 days
To evaluate the effects of the kynurenine pathway on brain injury after cardiac arrest. Results showed that IDO?/? mice had significantly higher survival rates and better neurological function compared to wild-type mice, and kynurenine pathway activation was associated with brain injury.
Anesthesiology. 2023 Nov 1;139(5):628-645
Kynurenine/L-犬尿氨酸 动物研究
Animal study
L-Kynurenine dilates rat and human arteries via Kv7 channels in vascular smooth muscle. In rats, L-Kynurenine causes hypotension, but this can be partially counteracted by Kv7 channel inhibition[2].Administration of L-Kynurenine, 1 hour prior to hypoxia-ischemia, demonstrated significant dose-dependent neuroprotection, with a dose of 300 mg/kg providing complete protection, and also prevented the induction of the c-fos immune response in the cerebral cortex[3].
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