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Selenium alleviates lipopolysaccharide-induced endometritis via regulating the recruitment of TLR4 into lipid rafts in mice

Abstract

Selenium (Se) is an essential trace element for living organisms, which plays diverse biological effects. Endometritis is a common reproductive disorder in dairy cows, causing huge economic losses. In this study, we explored the effects of Se on lipopolysaccharide (LPS)-induced endometritis in mice and expound its underlying mechanism of action. We validated the anti-inflammatory effects of Se in vivo by establishing a mouse model of endometriosis induced by LPS. Se significantly reversed the LPS-induced uterine histopathological changes, MPO activity and inflammatory cytokines levels in vivo. Simultaneously, TLR4 and its downstream signaling pathways, the lipid raft and cholesterol levels in the tissues were also attenuated by Se under the stimulation of LPS. In addition, the molecular mechanism of Se anti-inflammatory was clarified in mouse endometrial epithelial cells. Se inhibited TLR4-mediated NF-κB and IRF3 signal transduction pathways to reduce the production of inflammatory factors. We found that Se promoted the consumption of cholesterol to suppress the lipid rafts coming into being, and inhibited the TLR4 positioning to the lipid raft to prevent the inflammatory response caused by LPS. Meanwhile, Se activated the LxRα-ABCA1 pathway to cause the outflow of cholesterol in cell. The anti-inflammatory effect of Se was disrupted by silencing LxRα. In conclusion, Se exerted anti-inflammatory effects most likely by the LxRα-ABCA1 pathway activation, which inhibited lipid rafts by depleting cholesterol and ultimately impeded the migration of TLR4 to lipid rafts.

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Publication details

The article was received on 15 Oct 2019, accepted on 23 Nov 2019 and first published on 25 Nov 2019


Article type: Paper
DOI: 10.1039/C9FO02415H
Food Funct., 2019, Accepted Manuscript

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    Selenium alleviates lipopolysaccharide-induced endometritis via regulating the recruitment of TLR4 into lipid rafts in mice

    Y. Chen, Y. Zhao, J. Yang, H. Jing, W. Liang, M. Chen, M. yang, Y. wang and M. Guo, Food Funct., 2019, Accepted Manuscript , DOI: 10.1039/C9FO02415H

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