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Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II

We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures. FCD t...

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Published in:Journal of neuroinflammation 2018-01, Vol.15 (1), p.27-27, Article 27
Main Authors: Zhang, Zhongbin, Liu, Qingzhu, Liu, Ming, Wang, Hui, Dong, Ying, Ji, Taoyun, Liu, Xiaoyan, Jiang, Yuwu, Cai, Lixin, Wu, Ye
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container_title Journal of neuroinflammation
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creator Zhang, Zhongbin
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Wu, Ye
description We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures. FCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed. The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures. The HMGB1-TLR4 pathway was upregulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream pro-inflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified.
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FCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed. The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures. 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Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified.</description><subject>Astrocytes</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Dysplasia</subject><subject>FCD type II</subject><subject>Genetic aspects</subject><subject>HMGB1-TLR4</subject><subject>Inflammation</subject><subject>Neurons</subject><subject>Physiological aspects</subject><subject>Toll-like receptors</subject><subject>Upregulation</subject><issn>1742-2094</issn><issn>1742-2094</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptkk1v1DAQhiMEoqXwA7igSFy4pPgzti9IbUXblRYhQXu2Jo69dZXEwc6C8u_rkFJ1JeSDR-N3Hs-M3qJ4j9EpxrL-nDBRglUIywojISv5ojjGgpGKIMVePouPijcp3SNECa_J6-KIKCoJJfK4-Hk7RrvbdzD5MJTBldffrs5xdbP9wUo_uA76HqYQ53KE6e4PzDlZumCgK02Ik1-Cdk5jB8lDOc2jLTebt8UrB12y7x7vk-L28uvNxXW1_X61uTjbVoZTMlVMcMZd3XCnaM2NoMYKR5gSGBimdS1VHq7hmFqQtFZ1ywVtwLbSKGCGGnpSbFZuG-Bej9H3EGcdwOu_iRB3GpYeO6sBCcGV4pxyyTBSTdMi4WpwWFKEhcysLytr3De9bY0dpgjdAfTwZfB3ehd-ay4UznvOgE-PgBh-7W2adO-TsV0Hgw37pLFS-SeEOM3Sj6t0B7m1vOWQiWaR6zNOuGASE5RVp_9R5dPa3pswWOdz_qAArwUmhpSidU_dY6QXv-jVLzr7RS9-0cvYH56P_VTxzyD0AT6JuC0</recordid><startdate>20180130</startdate><enddate>20180130</enddate><creator>Zhang, Zhongbin</creator><creator>Liu, Qingzhu</creator><creator>Liu, Ming</creator><creator>Wang, Hui</creator><creator>Dong, Ying</creator><creator>Ji, Taoyun</creator><creator>Liu, Xiaoyan</creator><creator>Jiang, Yuwu</creator><creator>Cai, Lixin</creator><creator>Wu, Ye</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20180130</creationdate><title>Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II</title><author>Zhang, Zhongbin ; Liu, Qingzhu ; Liu, Ming ; Wang, Hui ; Dong, Ying ; Ji, Taoyun ; Liu, Xiaoyan ; Jiang, Yuwu ; Cai, Lixin ; Wu, Ye</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-47545f6b5f9365c73ce7f24971a4136689974b513ea83696d573baed8c9a4c3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Astrocytes</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Dysplasia</topic><topic>FCD type II</topic><topic>Genetic aspects</topic><topic>HMGB1-TLR4</topic><topic>Inflammation</topic><topic>Neurons</topic><topic>Physiological aspects</topic><topic>Toll-like receptors</topic><topic>Upregulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhongbin</creatorcontrib><creatorcontrib>Liu, Qingzhu</creatorcontrib><creatorcontrib>Liu, Ming</creatorcontrib><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Dong, Ying</creatorcontrib><creatorcontrib>Ji, Taoyun</creatorcontrib><creatorcontrib>Liu, Xiaoyan</creatorcontrib><creatorcontrib>Jiang, Yuwu</creatorcontrib><creatorcontrib>Cai, Lixin</creatorcontrib><creatorcontrib>Wu, Ye</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Journal of neuroinflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zhongbin</au><au>Liu, Qingzhu</au><au>Liu, Ming</au><au>Wang, Hui</au><au>Dong, Ying</au><au>Ji, Taoyun</au><au>Liu, Xiaoyan</au><au>Jiang, Yuwu</au><au>Cai, Lixin</au><au>Wu, Ye</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II</atitle><jtitle>Journal of neuroinflammation</jtitle><addtitle>J Neuroinflammation</addtitle><date>2018-01-30</date><risdate>2018</risdate><volume>15</volume><issue>1</issue><spage>27</spage><epage>27</epage><pages>27-27</pages><artnum>27</artnum><issn>1742-2094</issn><eissn>1742-2094</eissn><abstract>We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures. FCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed. The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures. The HMGB1-TLR4 pathway was upregulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream pro-inflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>29382328</pmid><doi>10.1186/s12974-018-1078-8</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Astrocytes
Cytokines
Development and progression
Dysplasia
FCD type II
Genetic aspects
HMGB1-TLR4
Inflammation
Neurons
Physiological aspects
Toll-like receptors
Upregulation
title Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II
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