NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB

Nuclear factor E2-related factor 2 (NRF2) plays an anti-inflammatory role in several pathological processes, but its function in lipopolysaccharide- (LPS-) induced goat endometrial epithelial cells (gEECs) is still unknown. We designed a study to investigate the function of NRF2 in LPS-induced gEECs...

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Autores principales:	Hongchu Bao, Qinglan Qu, Wei Zhang, Xinrong Wang, Jianye Fang, Jinwen Xue, Zhenteng Liu, Shunzhi He
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Pathology RB1-214
Acceso en línea:	https://doaj.org/article/f28a2942de694d4d839e3c749bfab8f2
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spelling	oai:doaj.org-article:f28a2942de694d4d839e3c749bfab8f22021-11-15T01:19:16ZNRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB1466-186110.1155/2021/9960721https://doaj.org/article/f28a2942de694d4d839e3c749bfab8f22021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9960721https://doaj.org/toc/1466-1861Nuclear factor E2-related factor 2 (NRF2) plays an anti-inflammatory role in several pathological processes, but its function in lipopolysaccharide- (LPS-) induced goat endometrial epithelial cells (gEECs) is still unknown. We designed a study to investigate the function of NRF2 in LPS-induced gEECs. LPS was found to increase the NRF2 expression and the nuclear abundance of NRF2 in gEECs in a dose-dependent manner. NRF2 knockout (KO) not only increased the expression of LPS-induced proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) but also increased the expression of TLR4, p-IκBα/IκBα, and p-p65/p65 proteins. Immunoprecipitation experiments showed that NRF2 directly binds to p65 in the nucleus and inhibits the binding of p65 to downstream target genes (TNF-α, IL-1β, IL-6, and IL-8). Even though a NF-κB/p65 inhibitor (PDTC) reduced the LPS-induced NRF2 expression and nuclear abundance of NRF2, overexpressing TNF-α reversed the inhibitory effects of PDTC on the NRF2 expression and on its abundance in the nucleus. Similarly, knockdown of the proinflammatory cytokines (TNF-α, IL-1β, IL-6, or IL-8) significantly decreased the LPS-induced NRF2 expression and NRF2 in the nucleus. In conclusion, our data suggest that proinflammatory cytokines induced by LPS through the TLR4/NF-κB pathway promote the NRF2 expression and its translocation into the nucleus. Our work also suggests that NRF2 inhibits the expression of proinflammatory cytokines by directly binding to p65.Hongchu BaoQinglan QuWei ZhangXinrong WangJianye FangJinwen XueZhenteng LiuShunzhi HeHindawi LimitedarticlePathologyRB1-214ENMediators of Inflammation, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214
spellingShingle	Pathology RB1-214 Hongchu Bao Qinglan Qu Wei Zhang Xinrong Wang Jianye Fang Jinwen Xue Zhenteng Liu Shunzhi He NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
description	Nuclear factor E2-related factor 2 (NRF2) plays an anti-inflammatory role in several pathological processes, but its function in lipopolysaccharide- (LPS-) induced goat endometrial epithelial cells (gEECs) is still unknown. We designed a study to investigate the function of NRF2 in LPS-induced gEECs. LPS was found to increase the NRF2 expression and the nuclear abundance of NRF2 in gEECs in a dose-dependent manner. NRF2 knockout (KO) not only increased the expression of LPS-induced proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) but also increased the expression of TLR4, p-IκBα/IκBα, and p-p65/p65 proteins. Immunoprecipitation experiments showed that NRF2 directly binds to p65 in the nucleus and inhibits the binding of p65 to downstream target genes (TNF-α, IL-1β, IL-6, and IL-8). Even though a NF-κB/p65 inhibitor (PDTC) reduced the LPS-induced NRF2 expression and nuclear abundance of NRF2, overexpressing TNF-α reversed the inhibitory effects of PDTC on the NRF2 expression and on its abundance in the nucleus. Similarly, knockdown of the proinflammatory cytokines (TNF-α, IL-1β, IL-6, or IL-8) significantly decreased the LPS-induced NRF2 expression and NRF2 in the nucleus. In conclusion, our data suggest that proinflammatory cytokines induced by LPS through the TLR4/NF-κB pathway promote the NRF2 expression and its translocation into the nucleus. Our work also suggests that NRF2 inhibits the expression of proinflammatory cytokines by directly binding to p65.
format	article
author	Hongchu Bao Qinglan Qu Wei Zhang Xinrong Wang Jianye Fang Jinwen Xue Zhenteng Liu Shunzhi He
author_facet	Hongchu Bao Qinglan Qu Wei Zhang Xinrong Wang Jianye Fang Jinwen Xue Zhenteng Liu Shunzhi He
author_sort	Hongchu Bao
title	NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
title_short	NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
title_full	NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
title_fullStr	NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
title_full_unstemmed	NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB
title_sort	nrf2 exerts anti-inflammatory effects in lps-induced geecs by inhibiting the activation of the nf-κb
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/f28a2942de694d4d839e3c749bfab8f2
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NRF2 Exerts Anti-Inflammatory Effects in LPS-Induced gEECs by Inhibiting the Activation of the NF-κB

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