Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis
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...
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2021
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oai:doaj.org-article:1eeeb8fbc9e14e8492af385c9cd68c3b2021-11-24T06:30:48ZSerum profiles of tryptophan-kynurenine pathway metabolites in psoriasis10.37349/ei.2021.000172768-6655https://doaj.org/article/1eeeb8fbc9e14e8492af385c9cd68c3b2021-10-01T00:00:00Zhttps://www.explorationpub.com/Journals/ei/Article/100317https://doaj.org/toc/2768-6655Aim: 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, catabolic enzyme from KYN or 3HK to downstream. 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.Mariko SeishimaYasuko YamamotoMasashi SakuraiRika SakaiKento FujiiYoko MizutaniKuniaki SaitoOpen Exploration Publishing Inc.articlepsoriasiskynureninasekynurenine metabolitetryptophan-kynurenine pathwayindoleamine 23-dioxygenaseImmunologic diseases. AllergyRC581-607ENExploration of Immunology, Vol 1, Iss 4, Pp 258-268 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
psoriasis kynureninase kynurenine metabolite tryptophan-kynurenine pathway indoleamine 2 3-dioxygenase Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
psoriasis kynureninase kynurenine metabolite tryptophan-kynurenine pathway indoleamine 2 3-dioxygenase Immunologic diseases. Allergy RC581-607 Mariko Seishima Yasuko Yamamoto Masashi Sakurai Rika Sakai Kento Fujii Yoko Mizutani Kuniaki Saito Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| description |
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, catabolic enzyme from KYN or 3HK to downstream. 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. |
| format |
article |
| author |
Mariko Seishima Yasuko Yamamoto Masashi Sakurai Rika Sakai Kento Fujii Yoko Mizutani Kuniaki Saito |
| author_facet |
Mariko Seishima Yasuko Yamamoto Masashi Sakurai Rika Sakai Kento Fujii Yoko Mizutani Kuniaki Saito |
| author_sort |
Mariko Seishima |
| title |
Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_short |
Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_full |
Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_fullStr |
Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_full_unstemmed |
Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_sort |
serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| publisher |
Open Exploration Publishing Inc. |
| publishDate |
2021 |
| url |
https://doaj.org/article/1eeeb8fbc9e14e8492af385c9cd68c3b |
| work_keys_str_mv |
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| _version_ |
1718415900956164096 |