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Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model

INTRODUCTION: 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 th...

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Autores principales: Takashima, Miyuki, Lalonde, Christian, Olszanski, Laura Ashley, Zhao, Feng-Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387587/
https://www.ncbi.nlm.nih.gov/pubmed/34456581
http://dx.doi.org/10.2147/JIR.S313799
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author Takashima, Miyuki
Lalonde, Christian
Olszanski, Laura Ashley
Zhao, Feng-Qi
author_facet Takashima, Miyuki
Lalonde, Christian
Olszanski, Laura Ashley
Zhao, Feng-Qi
author_sort Takashima, Miyuki
collection PubMed
description INTRODUCTION: 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 INFΥ, 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.
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spelling pubmed-83875872021-08-26 Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model Takashima, Miyuki Lalonde, Christian Olszanski, Laura Ashley Zhao, Feng-Qi J Inflamm Res Original Research INTRODUCTION: 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 INFΥ, 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. Dove 2021-08-21 /pmc/articles/PMC8387587/ /pubmed/34456581 http://dx.doi.org/10.2147/JIR.S313799 Text en © 2021 Takashima et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Takashima, Miyuki
Lalonde, Christian
Olszanski, Laura Ashley
Zhao, Feng-Qi
Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title 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_short Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model
title_sort localized and systemic inflammatory mediators in a murine acute mastitis model
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387587/
https://www.ncbi.nlm.nih.gov/pubmed/34456581
http://dx.doi.org/10.2147/JIR.S313799
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