IMR Press / FBL / Volume 20 / Issue 7 / DOI: 10.2741/4363

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Review
Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune activation
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1 Division of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2 Division of Cardiology and Endocrinology, Department of Internal Medicine, Hubei Provincial Corps Hospital, Chinese People’s Armed Police Forces, Wuhan, Hubei 430061, China
Front. Biosci. (Landmark Ed) 2015, 20(7), 1116–1143; https://doi.org/10.2741/4363
Published: 1 June 2015
Abstract

The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.

Keywords
Kynurenines
Cardiovascular Diseases
Inflammation
Oxidative Stress
Immune Activation
Review
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