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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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2021-10-01
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| Series: | Exploration of Immunology |
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| Online Access: | https://www.explorationpub.com/Journals/ei/Article/100317 |
| _version_ | 1818737678013693952 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T00:56:51Z |
| format | Article |
| id | doaj.art-1eeeb8fbc9e14e8492af385c9cd68c3b |
| institution | Directory Open Access Journal |
| issn | 2768-6655 |
| language | English |
| last_indexed | 2024-12-18T00:56:51Z |
| publishDate | 2021-10-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Immunology |
| spelling | doaj.art-1eeeb8fbc9e14e8492af385c9cd68c3b2022-12-21T21:26:28ZengOpen Exploration Publishing Inc.Exploration of Immunology2768-66552021-10-011425826810.37349/ei.2021.00017Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasisMariko Seishima0https://orcid.org/0000-0003-0007-3632Yasuko Yamamoto1https://orcid.org/0000-0003-2243-2800Masashi Sakurai2https://orcid.org/0000-0003-2717-0950Rika Sakai3Kento Fujii4https://orcid.org/0000-0003-2000-9451Yoko Mizutani5Kuniaki Saito6Department of Dermatology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan; Department of Dermatology, Asahi University Hospital, Hashimoto-cho 3-23, Gifu 500-8523, JapanDepartment of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, JapanDepartment of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, JapanDepartment of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, JapanDepartment of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, JapanAim: 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.https://www.explorationpub.com/Journals/ei/Article/100317psoriasiskynureninasekynurenine metabolitetryptophan-kynurenine pathwayindoleamine 23-dioxygenase |
| spellingShingle | Mariko Seishima Yasuko Yamamoto Masashi Sakurai Rika Sakai Kento Fujii Yoko Mizutani Kuniaki Saito Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis Exploration of Immunology psoriasis kynureninase kynurenine metabolite tryptophan-kynurenine pathway indoleamine 2 3-dioxygenase |
| title | 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_short | Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis |
| title_sort | serum profiles of tryptophan kynurenine pathway metabolites in psoriasis |
| topic | psoriasis kynureninase kynurenine metabolite tryptophan-kynurenine pathway indoleamine 2 3-dioxygenase |
| url | https://www.explorationpub.com/Journals/ei/Article/100317 |
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