Lysophosphatidylcholine induces glial cell activation: Role of rho kinase
Identifieur interne : 001D81 ( Istex/Corpus ); précédent : 001D80; suivant : 001D82Lysophosphatidylcholine induces glial cell activation: Role of rho kinase
Auteurs : Abdullah Md. Sheikh ; Atsushi Nagai ; Jae K. Ryu ; James G. Mclarnon ; Seung U. Kim ; Junichi MasudaSource :
- Glia [ 0894-1491 ] ; 2009-06.
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Abstract
Lysophosphatidylcholine (LPC), a major phospholipid component of atherogenic oxidized LDL, is implicated in atherosclerosis and, recently, in neurodegenerative diseases. We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL‐1β, COX‐2, and GM‐CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. Overall, our results indicate that LPC induced considerable neuroinflammatory reactivity in glia mediated by rho kinase‐dependent pathways with inhibition of these pathways conferring significant extents of neuroprotection. © 2008 Wiley‐Liss, Inc.
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DOI: 10.1002/glia.20815
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We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL‐1β, COX‐2, and GM‐CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. 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We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL‐1β, COX‐2, and GM‐CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. 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We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL‐1β, COX‐2, and GM‐CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. 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Vancouver, British Columbia, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="CA" type="organization"><unparsedAffiliation>Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">neurodegeneration</keyword><keyword xml:id="kwd2">astrocytes</keyword><keyword xml:id="kwd3">microglia</keyword><keyword xml:id="kwd4">neuroinflammation</keyword><keyword xml:id="kwd5">cytokine</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Lysophosphatidylcholine (LPC), a major phospholipid component of atherogenic oxidized LDL, is implicated in atherosclerosis and, recently, in neurodegenerative diseases. We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an <i>in vivo</i> rat model, and <i>in vitro</i> culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. <i>In vitro</i> studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors <i>IL‐1β</i>, <i>COX‐2</i>, and <i>GM‐CSF</i>. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. Overall, our results indicate that LPC induced considerable neuroinflammatory reactivity in glia mediated by rho kinase‐dependent pathways with inhibition of these pathways conferring significant extents of neuroprotection. © 2008 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Lysophosphatidylcholine induces glial cell activation: Role of rho kinase</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>LPC Induces Glial Activation</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Lysophosphatidylcholine induces glial cell activation: Role of rho kinase</title></titleInfo><name type="personal"><namePart type="given">Abdullah Md.</namePart><namePart type="family">Sheikh</namePart><affiliation>Department of Laboratory Medicine, Shimane University School of Medicine, 89‐1 Enya cho, Izumo 693‐8501, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Atsushi</namePart><namePart type="family">Nagai</namePart><affiliation>Department of Laboratory Medicine, Shimane University School of Medicine, 89‐1 Enya cho, Izumo 693‐8501, Japan</affiliation><affiliation>Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89‐1 Enya cho, Izumo 693‐8501, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jae K.</namePart><namePart type="family">Ryu</namePart><affiliation>Department of Medicine, Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><affiliation>Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James G.</namePart><namePart type="family">McLarnon</namePart><affiliation>Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Seung U.</namePart><namePart type="family">Kim</namePart><affiliation>Department of Medicine, Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Junichi</namePart><namePart type="family">Masuda</namePart><affiliation>Department of Laboratory Medicine, Shimane University School of Medicine, 89‐1 Enya cho, Izumo 693‐8501, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-06</dateIssued><dateCaptured encoding="w3cdtf">2008-02-06</dateCaptured><dateValid encoding="w3cdtf">2008-10-09</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">8</extent><extent unit="tables">2</extent><extent unit="references">44</extent><extent unit="words">7375</extent></physicalDescription><abstract lang="en">Lysophosphatidylcholine (LPC), a major phospholipid component of atherogenic oxidized LDL, is implicated in atherosclerosis and, recently, in neurodegenerative diseases. We investigated the immunomodulatory functions of LPC in the central nervous system (CNS) using both an in vivo rat model, and in vitro culture systems of human primary astrocytes and a microglia cell line, HMO6. Compared with PBS injection, 20 nmol LPC‐injection into the rat striatum increased astrocyte and microglial accumulation and elevated iNOS expression; concomitantly a time‐dependent decrease in number of neurons was exhibited. In vitro studies on astrocytes and HMO6 cells showed that LPC increased the gene expression of proinflammatory factors IL‐1β, COX‐2, and GM‐CSF. LPC also induced chemotactic responses in HMO6 cells. Inhibition of rho kinase by fasudil, Y27632, or expressing a dominant negative form of rho kinase inhibited the LPC‐induced IL‐1β mRNA expression in both astrocytes and HMO6. Moreover, intraperitoneal fasudil injection inhibited the LPC‐induced microglial accumulation and iNOS expression and also was effective in protecting against neuronal loss. Silencing G2A, a specific receptor for LPC, inhibited proinflammatory gene expression and HMO6 migration. Overall, our results indicate that LPC induced considerable neuroinflammatory reactivity in glia mediated by rho kinase‐dependent pathways with inhibition of these pathways conferring significant extents of neuroprotection. © 2008 Wiley‐Liss, Inc.</abstract><subject lang="en"><genre>keywords</genre><topic>neurodegeneration</topic><topic>astrocytes</topic><topic>microglia</topic><topic>neuroinflammation</topic><topic>cytokine</topic></subject><relatedItem type="host"><titleInfo><title>Glia</title></titleInfo><titleInfo type="abbreviated"><title>Glia</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0894-1491</identifier><identifier type="eISSN">1098-1136</identifier><identifier type="DOI">10.1002/(ISSN)1098-1136</identifier><identifier type="PublisherID">GLIA</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>57</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>898</start><end>907</end><total>10</total></extent></part></relatedItem><identifier type="istex">22E8596F50555FB0AD94257C033D76B34FD8DE8A</identifier><identifier type="DOI">10.1002/glia.20815</identifier><identifier type="ArticleID">GLIA20815</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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