Identifying lysophosphatidic acid receptor subtype 1 (LPA(1)) as a novel factor to modulate microglial activation and their TNF-alpha production by activating ERK1/2
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kwon, Jin Hyun | - |
dc.contributor.author | Gaire, Bhakta Prasad | - |
dc.contributor.author | Park, Se Jin | - |
dc.contributor.author | Shin, Dong-Yoon | - |
dc.contributor.author | Choi, Ji Woong | - |
dc.date.available | 2020-02-27T09:40:43Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2018-10 | - |
dc.identifier.issn | 1388-1981 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3239 | - |
dc.description.abstract | Microglia regulate immune responses in the brain, and their activation is key to the pathogenesis of diverse neurological diseases. Receptor-mediated lysophosphatidic acid (LPA) signaling has been known to regulate microglial biology, but it is still unclear which receptor subtypes guide the biology, particularly, microglial activation. Here, we investigated the pathogenic aspects of LPA receptor subtype 1 (LPA(1)) in microglial activation using a systemic lipopolysaccharide (LPS) administration-induced septic mouse model in vivo and LPS-stimulated rat primary microglia in vitro. LPA(1) knockdown in the brain with its specific shRNA lentivirus attenuated the sepsis-induced microglia activation, morphological transformation, and proliferation. LPA(1) knockdown also resulted in the downregulation of TNF-alpha, at both mRNA and protein levels in septic brains, but not IL-1 beta or IL-6. In rat primary microglia, genetic or pharmacological blockade of LPA(1) attenuated gene up regulation and secretion of TNF-alpha in LPS-stimulated cells. In particular, the latter was associated with the suppressed TNF-alpha converting enzyme (TACE) activity. We reaffirmed these biological aspects using a BV2 microglial cell line in which LPAI expression was negligible. LPA(1) overexpression in BV2 cells led to significant increments in TNF-alpha production upon stimulation with LPS, whereas inhibiting LPA(1) reversed the production. We further identified ERK1/2, but not p38 MAPK or Akt, as the underlying effector pathway after LPA(1) activation in both septic brains and stimulated microglia. The current findings of the novel role of LPA(1) in microglial activation along with its mechanistic aspects could be applied to understanding the pathogenesis of diverse neurological diseases that involve microglial activation. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.relation.isPartOf | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | - |
dc.subject | NECROSIS-FACTOR-ALPHA | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | CELL-LINE | - |
dc.subject | LYSOPHOSPHOLIPIDS | - |
dc.subject | RELEASE | - |
dc.subject | MOUSE | - |
dc.subject | LIPOPOLYSACCHARIDE | - |
dc.subject | POLARIZATION | - |
dc.subject | CHANNELS | - |
dc.subject | KINASE | - |
dc.title | Identifying lysophosphatidic acid receptor subtype 1 (LPA(1)) as a novel factor to modulate microglial activation and their TNF-alpha production by activating ERK1/2 | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000445310000008 | - |
dc.identifier.doi | 10.1016/j.bbalip.2018.07.015 | - |
dc.identifier.bibliographicCitation | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v.1863, no.10, pp.1237 - 1245 | - |
dc.identifier.scopusid | 2-s2.0-85051133271 | - |
dc.citation.endPage | 1245 | - |
dc.citation.startPage | 1237 | - |
dc.citation.title | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | - |
dc.citation.volume | 1863 | - |
dc.citation.number | 10 | - |
dc.contributor.affiliatedAuthor | Kwon, Jin Hyun | - |
dc.contributor.affiliatedAuthor | Gaire, Bhakta Prasad | - |
dc.contributor.affiliatedAuthor | Shin, Dong-Yoon | - |
dc.contributor.affiliatedAuthor | Choi, Ji Woong | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | LPA(1) | - |
dc.subject.keywordAuthor | Septic brain | - |
dc.subject.keywordAuthor | Microglia | - |
dc.subject.keywordAuthor | TNF-alpha | - |
dc.subject.keywordAuthor | TACE | - |
dc.subject.keywordAuthor | ERK1/2 | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | CELL-LINE | - |
dc.subject.keywordPlus | LYSOPHOSPHOLIPIDS | - |
dc.subject.keywordPlus | RELEASE | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordPlus | LIPOPOLYSACCHARIDE | - |
dc.subject.keywordPlus | POLARIZATION | - |
dc.subject.keywordPlus | CHANNELS | - |
dc.subject.keywordPlus | KINASE | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.