Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium

Noleto, Pablo G.; E., João Paulo; Sheldon, I. Martin; Sheldon, Martin

doi:10.3168/jds.2016-12023

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Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium

Pablo G. Noleto, João Paulo E. Saut, I. Martin Sheldon, Martin Sheldon

Journal of Dairy Science, Volume: 100, Pages: 2207 - 2212

Swansea University Author: Martin Sheldon

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DOI (Published version): 10.3168/jds.2016-12023

Abstract

Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL...

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Published in:	Journal of Dairy Science
ISSN:	00220302
Published:	2017
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URI:	https://cronfa.swan.ac.uk/Record/cronfa31648
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spelling	2018-01-12T10:48:36.8228427 v2 31648 2017-01-19 Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium ab0f74b794e59cc270c69e63ee1d9748 0000-0001-7902-5558 Martin Sheldon Martin Sheldon true false 2017-01-19 BMS Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL-1β and IL-6 and the chemokine IL-8. However, animals often fail to clear invading bacteria and develop uterine disease if they are in negative energy balance, with reduced abundance of glucose and glutamine, which are substrates for energy in tissues. Depletion of glucose blunts inflammatory responses in the endometrium, but the role of glutamine is not clear. The present study tested the hypothesis that depletion of glutamine compromises inflammatory responses to LPS in endometrial tissue. Ex vivo organ cultures of endometrium were challenged with LPS, and culture supernatants accumulated IL-1β, IL-6, and IL-8, as expected. However, reducing the availability of glutamine in culture medium containing glucose reduced the accumulation of IL-1β, IL-6, and IL-8 by >50%. Surprisingly, in the absence of glucose, supplying increasing amounts of glutamine was not sufficient to augment inflammatory responses to LPS, whereas, in the absence of glutamine, supplying more glucose increased inflammation. Furthermore, inhibiting glycolysis reduced the accumulation of IL-1β, IL-6, and IL-8 by >50%, even when glutamine and glucose were abundant. In conclusion, depletion of glutamine reduces inflammatory responses to LPS in the endometrium, and the activity of glutamine depends on glucose and glycolysis. These data provide mechanistic insights into how negative energy balance may be linked to postpartum uterine disease. Journal Article Journal of Dairy Science 100 2207 2212 00220302 21 2 2017 2017-02-21 10.3168/jds.2016-12023 The work was funded by a project grant to IMS bythe Biotechnology and Biological Sciences ResearchCouncil (BB/I017240/1; Swindon, UK). Coordenacaode Aperfeicoamento de Pessoal de Nivel Superior(99999.010219/2014-05; Brasilia, Brazil) and ConselhoNacional de Desenvolvimento Cientifico e Tecnologico(486143/2013-9; Brasilia, Brazil) were supported PGNand JPES. COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University RCUK, BBSRC, BB/I017240/1 2018-01-12T10:48:36.8228427 2017-01-19T13:31:30.3080097 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Pablo G. Noleto 1 João Paulo E. Saut 2 I. Martin Sheldon 3 Martin Sheldon 0000-0001-7902-5558 4 0031648-21022017093917.pdf JDSNoletov2.pdf 2017-02-21T09:39:17.7070000 Output 462546 application/pdf Version of Record true 2017-02-21T00:00:00.0000000 This is an open access article under the CC BY 2.0 license (http://creativecommons.org/licenses/by/2.0/). true eng
title	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
spellingShingle	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium Martin Sheldon
title_short	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
title_full	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
title_fullStr	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
title_full_unstemmed	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
title_sort	Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium
author_id_str_mv	ab0f74b794e59cc270c69e63ee1d9748
author_id_fullname_str_mv	ab0f74b794e59cc270c69e63ee1d9748_***_Martin Sheldon
author	Martin Sheldon
author2	Pablo G. Noleto João Paulo E. Saut I. Martin Sheldon Martin Sheldon
format	Journal article
container_title	Journal of Dairy Science
container_volume	100
container_start_page	2207
publishDate	2017
institution	Swansea University
issn	00220302
doi_str_mv	10.3168/jds.2016-12023
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL-1β and IL-6 and the chemokine IL-8. However, animals often fail to clear invading bacteria and develop uterine disease if they are in negative energy balance, with reduced abundance of glucose and glutamine, which are substrates for energy in tissues. Depletion of glucose blunts inflammatory responses in the endometrium, but the role of glutamine is not clear. The present study tested the hypothesis that depletion of glutamine compromises inflammatory responses to LPS in endometrial tissue. Ex vivo organ cultures of endometrium were challenged with LPS, and culture supernatants accumulated IL-1β, IL-6, and IL-8, as expected. However, reducing the availability of glutamine in culture medium containing glucose reduced the accumulation of IL-1β, IL-6, and IL-8 by >50%. Surprisingly, in the absence of glucose, supplying increasing amounts of glutamine was not sufficient to augment inflammatory responses to LPS, whereas, in the absence of glutamine, supplying more glucose increased inflammation. Furthermore, inhibiting glycolysis reduced the accumulation of IL-1β, IL-6, and IL-8 by >50%, even when glutamine and glucose were abundant. In conclusion, depletion of glutamine reduces inflammatory responses to LPS in the endometrium, and the activity of glutamine depends on glucose and glycolysis. These data provide mechanistic insights into how negative energy balance may be linked to postpartum uterine disease.
published_date	2017-02-21T03:38:41Z
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Short communication: Glutamine modulates inflammatory responses to lipopolysaccharide in ex vivo bovine endometrium

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