Fresh evidence overturns the identification of a factor involved in blood-vessel dilation

Kass, David A.

doi:10.1038/d41586-019-00508-z

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…Classical roles of KYN are immune tolerance, 9 tumor immune escape, 27–29,35 and the pathophysiology of neurological and psychiatric disturbances 10 . Recently, other functions were identified, such as blood vessel dilation 12 and microbiome/brain interaction 11 . In this study, we identified a new function for KYN on melanogenesis…”

Section: Discussionmentioning

confidence: 84%

“…We showed that skin is a target for a regulatory/physiological activity of KYN, and therefore IDO, on the biological phenomenon of pigmentation. The vast literature of KYN is mainly focused on immunomodulation, but recent studies show that KYN participates in a broad spectrum of biological processes 9–13,27–29 (Figure 3). Besides central nervous system cells, 10,11 immune cells 9 and tumor cells, 27–29,35 possible sources of KYN are melanocytes, keratinocytes and fibroblasts 26,36,37 .…”

Section: Discussionmentioning

confidence: 99%

“…KYN has crucial roles in immune regulation, 9 participation in the pathophysiology of neurological and psychiatric disturbances, 10 and infectious diseases 11 . Recent studies have identified new biological effects of KYN and downstream on vasodilatation 12 and bone remodelling 13 . Here, we addressed the effect of KYN on melanogenesis and whether pigmentation affects Trp metabolization.…”

Section: Introductionmentioning

confidence: 99%

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Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Branquinho

Silva

Castilho

et al. 2021

Experimental Dermatology

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Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co‐cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already known inhibitory effect promoted by IFN‐γ. Since increased KYN production depends on the IFN‐γ‐inducible enzyme indoleamine‐2,3‐dioxygenase (IDO), we propose that part of the effect of IFN‐γ on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN and downstream products along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Branquinho

Silva

Castilho

et al. 2021

Experimental Dermatology

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“…Kynurenine is an endogenous relaxing factor for blood vessels [ 92 , 171 ], and the TKP has been proposed as a therapeutic target in pre-eclampsia and other hypertensive disorders [ 172 , 173 ]. Further complexity has been recently evidenced, since IDO1 can regulate vascular tone in inflammation by producing singlet molecular oxygen and the Trp metabolite cis-WOOH (cis-hydroperoxide (2S,3aR,8aR)-3a-hydroperoxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid) [ 174 , 175 ]. Endothelial IDO1 is likely necessary for exerting vascular relaxation, and critical levels of endothelial and/or perivascular concentration of vasoactive Trp metabolites may be necessary for effective control of the vascular tone [ 176 ].…”

Section: Introductionmentioning

confidence: 99%

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

et al. 2022

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Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome’s evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.

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Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG

Nakamura¹,

Tsujita²

2021

Journal of Cardiology

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Fresh evidence overturns the identification of a factor involved in blood-vessel dilation

Cited by 3 publications

References 14 publications

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG

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