L-arginine as a novel target for clinical intervention in inflammatory bowel disease

Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and rep...

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Autores principales:	Björn Nüse, Jochen Mattner
Formato:	article
Lenguaje:	EN
Publicado:	Open Exploration Publishing Inc. 2021
Materias:	arginase-1 l-arginine inflammatory bowel disease colitis gut microbiota intestinal metabolism Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/795628a54bfe46eca020af5f2c59efd8
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spelling	oai:doaj.org-article:795628a54bfe46eca020af5f2c59efd82021-11-24T05:54:59ZL-arginine as a novel target for clinical intervention in inflammatory bowel disease10.37349/ei.2021.000082768-6655https://doaj.org/article/795628a54bfe46eca020af5f2c59efd82021-06-01T00:00:00Zhttps://www.explorationpub.com/Journals/ei/Article/10038https://doaj.org/toc/2768-6655Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses of Arg1 and the L-arginine metabolism in the immune system. Utilizing cell-specific conditional Arg1 knockouts, we have recently reported that Arg1, surprisingly, hampered the resolution of experimental colitis due to the restriction of the intraluminal availability of L-arginine. Reduced levels of L-arginine restrained the compositional diversity of the intestinal microbiota and subsequently the mutual metabolism between the microbiota and the host. Thus, the intraluminal microbiota represents a potential therapeutic target for L-arginine metabolism aside from host-dependent L-arginine consumption.Björn NüseJochen MattnerOpen Exploration Publishing Inc.articlearginase-1l-arginineinflammatory bowel diseasecolitisgut microbiotaintestinal metabolismImmunologic diseases. AllergyRC581-607ENExploration of Immunology, Vol 1, Iss 2, Pp 80-89 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arginase-1 l-arginine inflammatory bowel disease colitis gut microbiota intestinal metabolism Immunologic diseases. Allergy RC581-607
spellingShingle	arginase-1 l-arginine inflammatory bowel disease colitis gut microbiota intestinal metabolism Immunologic diseases. Allergy RC581-607 Björn Nüse Jochen Mattner L-arginine as a novel target for clinical intervention in inflammatory bowel disease
description	Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses of Arg1 and the L-arginine metabolism in the immune system. Utilizing cell-specific conditional Arg1 knockouts, we have recently reported that Arg1, surprisingly, hampered the resolution of experimental colitis due to the restriction of the intraluminal availability of L-arginine. Reduced levels of L-arginine restrained the compositional diversity of the intestinal microbiota and subsequently the mutual metabolism between the microbiota and the host. Thus, the intraluminal microbiota represents a potential therapeutic target for L-arginine metabolism aside from host-dependent L-arginine consumption.
format	article
author	Björn Nüse Jochen Mattner
author_facet	Björn Nüse Jochen Mattner
author_sort	Björn Nüse
title	L-arginine as a novel target for clinical intervention in inflammatory bowel disease
title_short	L-arginine as a novel target for clinical intervention in inflammatory bowel disease
title_full	L-arginine as a novel target for clinical intervention in inflammatory bowel disease
title_fullStr	L-arginine as a novel target for clinical intervention in inflammatory bowel disease
title_full_unstemmed	L-arginine as a novel target for clinical intervention in inflammatory bowel disease
title_sort	l-arginine as a novel target for clinical intervention in inflammatory bowel disease
publisher	Open Exploration Publishing Inc.
publishDate	2021
url	https://doaj.org/article/795628a54bfe46eca020af5f2c59efd8
work_keys_str_mv	AT bjornnuse larginineasanoveltargetforclinicalinterventionininflammatoryboweldisease AT jochenmattner larginineasanoveltargetforclinicalinterventionininflammatoryboweldisease
_version_	1718415919915466752

L-arginine as a novel target for clinical intervention in inflammatory bowel disease

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