Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model

Miyuki Takashima,1,2 Christian Lalonde,1 Laura Ashley Olszanski,1 Feng-Qi Zhao1 1Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, 05405, USA; 2Wakunaga Pharmaceutical Co. Ltd, Osaka, 532-0003, JapanCorrespondence: Feng-Qi Zhao Email fzhao@uvm.eduIntroduction: Milk...

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Autores principales:	Takashima M, Lalonde C, Olszanski LA, Zhao FQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cytokine lipopolysaccharide oxidative stress proteasome transcriptome change Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b6fdf15f59cd49fb8038f509e6b01991
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spelling	oai:doaj.org-article:b6fdf15f59cd49fb8038f509e6b019912021-12-02T17:08:57ZLocalized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model1178-7031https://doaj.org/article/b6fdf15f59cd49fb8038f509e6b019912021-08-01T00:00:00Zhttps://www.dovepress.com/localized-and-systemic-inflammatory-mediators-in-a-murine-acute-mastit-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Miyuki Takashima,1,2 Christian Lalonde,1 Laura Ashley Olszanski,1 Feng-Qi Zhao1 1Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, 05405, USA; 2Wakunaga Pharmaceutical Co. Ltd, Osaka, 532-0003, JapanCorrespondence: Feng-Qi Zhao Email fzhao@uvm.eduIntroduction: Milk depression is the major driver of economic loss due to mastitis in dairy animals. The aim of this study was to identify potential mediators of milk depression by investigating the local and systemic changes in gene expression or cytokine production during endotoxin challenge of the mammary gland in a mouse model.Methods: The left and right sides of the 4th pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, Escherichia coli 055: B5, 50 μL of 0.4 mg/mL) or sterile PBS through the teat meatus 3 days postpartum (n = 9). The 4th glands were individually collected 12 h after LPS injection and analyzed to identify gene expression changes by RNA sequencing and real-time PCR, and the plasma was collected before and after LPS challenge and analyzed to determine the levels of 32 cytokines.Results: Transcriptome analysis showed that in addition to strong pro-inflammatory responses, which included granulocyte and monocyte migration and cytokine production and signaling, the LPS-treated glands exhibited strong ubiquitin-mediated and immune-mediated proteasome activation and an increase in nitric oxide-mediated oxidative stress. Furthermore, LPS induced a down-regulation in vesicle membrane, vesicle-mediated trafficking, and metabolic processes of amino acids and other organic molecules in the mammary gland. Of the 32 cytokines analyzed, the levels of 24 (mainly IL-6, G-CSF, MCP-1, RANTES, MIG, MIP-1b, KC, MIP-2, IP-10, and TNFα) were increased or tended to increase in the blood after LPS treatment, and only the levels of IL-9 were decreased. In the mammary gland after LPS challenge, the levels of IL-5, IL-6, IP-10, LIF, MCP-1, MIP-2, and TNFα were significantly increased, and the levels of INF&Ugr;, IL-2, IL-4, IL-10, and IL-12 (p40) were decreased.Discussion: These observations provide potential markers and targets for further studies on the prevention and treatment of gram-negative bacteria-induced mastitis.Keywords: cytokine, lipopolysaccharide, oxidative stress, proteasome, transcriptome changeTakashima MLalonde COlszanski LAZhao FQDove Medical Pressarticlecytokinelipopolysaccharideoxidative stressproteasometranscriptome changePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4053-4067 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytokine lipopolysaccharide oxidative stress proteasome transcriptome change Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	cytokine lipopolysaccharide oxidative stress proteasome transcriptome change Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Takashima M Lalonde C Olszanski LA Zhao FQ Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
description	Miyuki Takashima,1,2 Christian Lalonde,1 Laura Ashley Olszanski,1 Feng-Qi Zhao1 1Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, 05405, USA; 2Wakunaga Pharmaceutical Co. Ltd, Osaka, 532-0003, JapanCorrespondence: Feng-Qi Zhao Email fzhao@uvm.eduIntroduction: Milk depression is the major driver of economic loss due to mastitis in dairy animals. The aim of this study was to identify potential mediators of milk depression by investigating the local and systemic changes in gene expression or cytokine production during endotoxin challenge of the mammary gland in a mouse model.Methods: The left and right sides of the 4th pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, Escherichia coli 055: B5, 50 μL of 0.4 mg/mL) or sterile PBS through the teat meatus 3 days postpartum (n = 9). The 4th glands were individually collected 12 h after LPS injection and analyzed to identify gene expression changes by RNA sequencing and real-time PCR, and the plasma was collected before and after LPS challenge and analyzed to determine the levels of 32 cytokines.Results: Transcriptome analysis showed that in addition to strong pro-inflammatory responses, which included granulocyte and monocyte migration and cytokine production and signaling, the LPS-treated glands exhibited strong ubiquitin-mediated and immune-mediated proteasome activation and an increase in nitric oxide-mediated oxidative stress. Furthermore, LPS induced a down-regulation in vesicle membrane, vesicle-mediated trafficking, and metabolic processes of amino acids and other organic molecules in the mammary gland. Of the 32 cytokines analyzed, the levels of 24 (mainly IL-6, G-CSF, MCP-1, RANTES, MIG, MIP-1b, KC, MIP-2, IP-10, and TNFα) were increased or tended to increase in the blood after LPS treatment, and only the levels of IL-9 were decreased. In the mammary gland after LPS challenge, the levels of IL-5, IL-6, IP-10, LIF, MCP-1, MIP-2, and TNFα were significantly increased, and the levels of INF&Ugr;, IL-2, IL-4, IL-10, and IL-12 (p40) were decreased.Discussion: These observations provide potential markers and targets for further studies on the prevention and treatment of gram-negative bacteria-induced mastitis.Keywords: cytokine, lipopolysaccharide, oxidative stress, proteasome, transcriptome change
format	article
author	Takashima M Lalonde C Olszanski LA Zhao FQ
author_facet	Takashima M Lalonde C Olszanski LA Zhao FQ
author_sort	Takashima M
title	Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_short	Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_full	Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_fullStr	Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_full_unstemmed	Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_sort	localized and systemic inflammatory mediators in a murine acute mastitis model
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b6fdf15f59cd49fb8038f509e6b01991
work_keys_str_mv	AT takashimam localizedandsystemicinflammatorymediatorsinamurineacutemastitismodel AT lalondec localizedandsystemicinflammatorymediatorsinamurineacutemastitismodel AT olszanskila localizedandsystemicinflammatorymediatorsinamurineacutemastitismodel AT zhaofq localizedandsystemicinflammatorymediatorsinamurineacutemastitismodel
_version_	1718381519515418624

Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model

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