Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

Abstract

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

Elevated circulating C‐X‐C motif chemokine ligand 1 DNA copies in psoriasis

“…4 Although the expression levels of CXCL1 messenger RNA are upregulated in the lesional skin of psoriasis, 4 serum CXCL1 protein levels are not increased compared with healthy controls. 5 The current study revealed that CXCL1 copies in cfDNA were significantly elevated in psoriasis and positively correlated with PASI score. Based on these findings, the measurement of circulating CXCL1 DNA copies is useful not only for the elucidation of the pathogenesis but also the diagnosis of psoriasis.…”

The Kynurenine/Tryptophan Ratio as a Promising Metabolomic Biomarker for Diagnosing the Spectrum of Tuberculosis Infection and Disease

“…In experimentally developed viral, bacterial, or parasite inside the cell or inflammation, plasma tryptophan levels have been shown to decrease or to raise kynurenine-tryptophan levels. 23 When the immune system is chronically activated, as in autoimmune disorders, 18 , 24 inflammatory diseases, 2 , 25 cancer, 14 , 26 and major trauma, tryptophan use has been reported to increase. The increase of metabolic intermediates including kynurenine and quinolinic acid in almost all of these investigations suggests tryptophan breakdown pathway participation.…”

Evaluation of Kynu, Defb2, Camp, and Penk Expression Levels as Psoriasis Marker in the Imiquimod‐Induced Psoriasis Model

“…Kynurenine (KYN) is a metabolite of tryptophan that reduces the expression of some inflammatory genes in keratinocytes [ 25 ]. It has been observed that the upregulation of KYNU leads to the destruction of KYN and induces excessive inflammation in psoriasis [ 27 ].…”