Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia

Context Icariin (ICA), a flavonol glycoside extracted from Epimedium brevicornum Maxim (Berberidaceae), has been proven to inhibit inflammatory response in ischaemic rats in our laboratory's previous work. However, its underlying mechanism is still unclear. Objective This study investigates the...

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Autores principales:	Zhen-Tao Mo, Jie Zheng, Yu-ling Liao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	microglia oxygen-glucose deprivation ire1 inflammation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/244f15e1d49b4648a249293a4cea6bf6
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spelling	oai:doaj.org-article:244f15e1d49b4648a249293a4cea6bf62021-11-04T15:00:42ZIcariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia1388-02091744-511610.1080/13880209.2021.1991959https://doaj.org/article/244f15e1d49b4648a249293a4cea6bf62021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1991959https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context Icariin (ICA), a flavonol glycoside extracted from Epimedium brevicornum Maxim (Berberidaceae), has been proven to inhibit inflammatory response in ischaemic rats in our laboratory's previous work. However, its underlying mechanism is still unclear. Objective This study investigates the effects of ICA on endoplasmic reticulum (ER) stress mediated inflammation induced by cerebral ischaemia–reperfusion (I/R) injury in vitro. Materials and methods The primary cultured microglia were treated with oxygen-glucose deprivation (OGD) for 2 h followed by a 24 h reoxygenation. ICA (0.37, 0.74 and 1.48 μmol/L) administration was performed 1 h prior OGD and acting through 2 h OGD. The control group was cultured in normal conditions. At 24 h after reoxygenation, the expression of IRE1α, XBP1u, XBP1s, NLRP3 and caspase-1 was detected by western blotting (WB) and quantitative real-time (qRT) PCR; the expression of p-IRE1α was examined by WB; the expression of IL-1β, IL-6 and TNF-α was measured by WB and enzyme-linked immunosorbent assay (ELISA). Results ICA (0.37, 0.74 and 1.48 μmol/L) reduced the ratio of p-IRE1α/IRE1α, the mRNA level of IRE1α, the expression of XBP1u, XBP1s, NLRP3, caspase-1 at both the mRNA and protein level expression of IL-1β, IL-6 and TNF-α in OGD/R injured microglia. Overexpression of IRE1 significantly reversed the effects of ICA. Discussion and conclusions These results suggested that ICA might decrease the expression of IL-1β, IL-6 and TNF-α by inhibiting IRE1/XBP1s pathway. The anti-inflammatory effect of ICA may provide a potential therapeutic strategy for the treatment of brain injury after stroke.Zhen-Tao MoJie ZhengYu-ling LiaoTaylor & Francis Grouparticlemicrogliaoxygen-glucose deprivationire1inflammationTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1473-1479 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microglia oxygen-glucose deprivation ire1 inflammation Therapeutics. Pharmacology RM1-950
spellingShingle	microglia oxygen-glucose deprivation ire1 inflammation Therapeutics. Pharmacology RM1-950 Zhen-Tao Mo Jie Zheng Yu-ling Liao Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
description	Context Icariin (ICA), a flavonol glycoside extracted from Epimedium brevicornum Maxim (Berberidaceae), has been proven to inhibit inflammatory response in ischaemic rats in our laboratory's previous work. However, its underlying mechanism is still unclear. Objective This study investigates the effects of ICA on endoplasmic reticulum (ER) stress mediated inflammation induced by cerebral ischaemia–reperfusion (I/R) injury in vitro. Materials and methods The primary cultured microglia were treated with oxygen-glucose deprivation (OGD) for 2 h followed by a 24 h reoxygenation. ICA (0.37, 0.74 and 1.48 μmol/L) administration was performed 1 h prior OGD and acting through 2 h OGD. The control group was cultured in normal conditions. At 24 h after reoxygenation, the expression of IRE1α, XBP1u, XBP1s, NLRP3 and caspase-1 was detected by western blotting (WB) and quantitative real-time (qRT) PCR; the expression of p-IRE1α was examined by WB; the expression of IL-1β, IL-6 and TNF-α was measured by WB and enzyme-linked immunosorbent assay (ELISA). Results ICA (0.37, 0.74 and 1.48 μmol/L) reduced the ratio of p-IRE1α/IRE1α, the mRNA level of IRE1α, the expression of XBP1u, XBP1s, NLRP3, caspase-1 at both the mRNA and protein level expression of IL-1β, IL-6 and TNF-α in OGD/R injured microglia. Overexpression of IRE1 significantly reversed the effects of ICA. Discussion and conclusions These results suggested that ICA might decrease the expression of IL-1β, IL-6 and TNF-α by inhibiting IRE1/XBP1s pathway. The anti-inflammatory effect of ICA may provide a potential therapeutic strategy for the treatment of brain injury after stroke.
format	article
author	Zhen-Tao Mo Jie Zheng Yu-ling Liao
author_facet	Zhen-Tao Mo Jie Zheng Yu-ling Liao
author_sort	Zhen-Tao Mo
title	Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
title_short	Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
title_full	Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
title_fullStr	Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
title_full_unstemmed	Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia
title_sort	icariin inhibits the expression of il-1β, il-6 and tnf-α induced by ogd/r through the ire1/xbp1s pathway in microglia
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/244f15e1d49b4648a249293a4cea6bf6
work_keys_str_mv	AT zhentaomo icariininhibitstheexpressionofil1bil6andtnfainducedbyogdrthroughtheire1xbp1spathwayinmicroglia AT jiezheng icariininhibitstheexpressionofil1bil6andtnfainducedbyogdrthroughtheire1xbp1spathwayinmicroglia AT yulingliao icariininhibitstheexpressionofil1bil6andtnfainducedbyogdrthroughtheire1xbp1spathwayinmicroglia
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Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia

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