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Pro-inflammatory cytokine TNF-alpha is a key inhibitory factor for lactose synthesis pathway in lactating mammary epithelial cells

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Title: Pro-inflammatory cytokine TNF-alpha is a key inhibitory factor for lactose synthesis pathway in lactating mammary epithelial cells
Authors: Kobayashi, Ken Browse this author →KAKEN DB
Kuki, Chinatsu Browse this author
Oyama, Shoko Browse this author
Kumura, Haruto Browse this author →KAKEN DB
Keywords: TNF-alpha
IL-1 beta
IL-6
Lactose
Mammary epithelial cell
GLUT1
Issue Date: 16-Jan-2016
Publisher: Elsevier
Journal Title: Experimental cell research
Volume: 340
Issue: 2
Start Page: 295
End Page: 304
Publisher DOI: 10.1016/j.yexcr.2015.10.030
PMID: 26518119
Abstract: Lactose is a milk-specific carbohydrate synthesized by mammary epithelial cells (MECs) in mammary glands during lactation. Lactose synthesis is downregulated under conditions causing inflammation such as mastitis, in which MECs are exposed to high concentrations of inflammatory cytokines. In this study, we investigated whether inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6) directly influence the lactose synthesis pathway by using two types of murine MEC culture models: the monolayer culture of MECs to induce lactogenesis; and the three-dimensional culture of MECs surrounded by Matrigel to induce reconstitution of the alveolar structure in vitro. TNF-alpha caused severe down-regulation of lactose synthesis related genes concurrently with the degradation of glucose transporter 1 (GLUTI) from the basolateral membranes in MECs. IL-1 beta also caused degradation of GLUTI along with a decrease in the expression level of beta-1,4-galactosylransferase 3. IL-6 caused both up-regulation and down-regulation of the expression levels of lactose synthesis-related genes in MECs. These results indicate that TNF-alpha, IL-1 beta, and IL-6 have different effects on the lactose synthesis pathway in MECs. Furthermore, TNF-alpha triggered activation of NFKB and inactivation of STAT5, suggesting that NF kappa B and STAT5 signaling pathways are involved in the multiple adverse effects of TNF-alpha on the lactose synthesis pathway. (C) 2015 Elsevier Inc. All rights reserved.
Rights: © [2015],Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/63261
Appears in Collections:農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 謙

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