Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.

Although they represent the cornerstone of analgesic therapy, opioids, such as morphine, are limited in efficacy by drug tolerance, hyperalgesia and other side effects. Activation of microglia and the consequent production of proinflammatory cytokines play a key pathogenic role in morphine tolerance...

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Autores principales:	Yaqiong Yang, Yu Sun, Rong Hu, Jia Yan, Ziheng Wang, Wenlong Li, Hong Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e01dcd0b4d3348d392cdb2905db4c659
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spelling	oai:doaj.org-article:e01dcd0b4d3348d392cdb2905db4c6592021-12-02T20:14:37ZMorphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.1932-620310.1371/journal.pone.0256870https://doaj.org/article/e01dcd0b4d3348d392cdb2905db4c6592021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256870https://doaj.org/toc/1932-6203Although they represent the cornerstone of analgesic therapy, opioids, such as morphine, are limited in efficacy by drug tolerance, hyperalgesia and other side effects. Activation of microglia and the consequent production of proinflammatory cytokines play a key pathogenic role in morphine tolerance, but the exact mechanisms are not well understood. This study aimed to investigate the regulatory mechanism of epidermal growth factor receptor (EGFR) on microglial activation induced by morphine in mouse microglial BV-2 cells. In this research, BV-2 cells were stimulated with morphine or pretreated with AG1478 (an inhibitor of EGFR). Expression levels of cluster of differentiation molecule 11b (CD11b), EGFR, and phospho-EGFR were detected by immunofluorescence staining. Cell signaling was assayed by Western blot. The migration ability of BV-2 cells was tested by Transwell assay. The production of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the cell supernatant was determined by ELISA. We observed that the expression of CD11b induced by morphine was increased in a dose- and time- dependent manner in BV-2 cells. Phosphorylation levels of EGFR and ERK1/2, migration of BV-2 cells, and production of IL-1β and TNFα were markedly enhanced by morphine treatment. The activation, migration, and production of proinflammatory cytokines in BV-2 cells were inhibited by blocking the EGFR signaling pathway with AG1478. The present study demonstrated that the EGFR/ERK signaling pathway may represent a novel pharmacological strategy to suppress morphine tolerance through attenuation of microglial activation.Yaqiong YangYu SunRong HuJia YanZiheng WangWenlong LiHong JiangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256870 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yaqiong Yang Yu Sun Rong Hu Jia Yan Ziheng Wang Wenlong Li Hong Jiang Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
description	Although they represent the cornerstone of analgesic therapy, opioids, such as morphine, are limited in efficacy by drug tolerance, hyperalgesia and other side effects. Activation of microglia and the consequent production of proinflammatory cytokines play a key pathogenic role in morphine tolerance, but the exact mechanisms are not well understood. This study aimed to investigate the regulatory mechanism of epidermal growth factor receptor (EGFR) on microglial activation induced by morphine in mouse microglial BV-2 cells. In this research, BV-2 cells were stimulated with morphine or pretreated with AG1478 (an inhibitor of EGFR). Expression levels of cluster of differentiation molecule 11b (CD11b), EGFR, and phospho-EGFR were detected by immunofluorescence staining. Cell signaling was assayed by Western blot. The migration ability of BV-2 cells was tested by Transwell assay. The production of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in the cell supernatant was determined by ELISA. We observed that the expression of CD11b induced by morphine was increased in a dose- and time- dependent manner in BV-2 cells. Phosphorylation levels of EGFR and ERK1/2, migration of BV-2 cells, and production of IL-1β and TNFα were markedly enhanced by morphine treatment. The activation, migration, and production of proinflammatory cytokines in BV-2 cells were inhibited by blocking the EGFR signaling pathway with AG1478. The present study demonstrated that the EGFR/ERK signaling pathway may represent a novel pharmacological strategy to suppress morphine tolerance through attenuation of microglial activation.
format	article
author	Yaqiong Yang Yu Sun Rong Hu Jia Yan Ziheng Wang Wenlong Li Hong Jiang
author_facet	Yaqiong Yang Yu Sun Rong Hu Jia Yan Ziheng Wang Wenlong Li Hong Jiang
author_sort	Yaqiong Yang
title	Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
title_short	Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
title_full	Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
title_fullStr	Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
title_full_unstemmed	Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.
title_sort	morphine promotes microglial activation by upregulating the egfr/erk signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e01dcd0b4d3348d392cdb2905db4c659
work_keys_str_mv	AT yaqiongyang morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT yusun morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT ronghu morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT jiayan morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT zihengwang morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT wenlongli morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway AT hongjiang morphinepromotesmicroglialactivationbyupregulatingtheegfrerksignalingpathway
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Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway.

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