S1P(1) Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gaire, Bhakta Prasad | - |
dc.contributor.author | Bae, Young Joo | - |
dc.contributor.author | Choi, Ji Woong | - |
dc.date.available | 2020-02-27T02:21:13Z | - |
dc.date.created | 2020-02-04 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.issn | 1976-9148 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/893 | - |
dc.description.abstract | M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor sub-type 1 (S1P(1)) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between S1P(1) and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of S1P(1) is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether S1P(1) was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing S1P(1) activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing S1P(1) activity with AUY954 administration inhibited M1-polarizatioin-relevant NF-kappa B activation in post-ischemic brain. Particularly, NF-kappa B activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through S1P(1) in post-ischemic brain mainly occurred in activated microglia. Suppressing S1P(1) activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that S1P(1) could also influence M2 polarization in post-ischemic brain. Finally, suppressing S1P(1 )activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevantAkt, all of which were downstream pathways following SIP, activation. Overall, these results revealed S1P(1)-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | KOREAN SOC APPLIED PHARMACOLOGY | - |
dc.relation.isPartOf | BIOMOLECULES & THERAPEUTICS | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | ACTIVATION | - |
dc.subject | FINGOLIMOD | - |
dc.subject | MICROGLIA | - |
dc.subject | SPHINGOSINE-1-PHOSPHATE | - |
dc.subject | NEUROGENESIS | - |
dc.subject | EXPRESSION | - |
dc.subject | STROKE | - |
dc.subject | INFLAMMATION | - |
dc.title | S1P(1) Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000493399700003 | - |
dc.identifier.doi | 10.4062/biomolther.2019.005 | - |
dc.identifier.bibliographicCitation | BIOMOLECULES & THERAPEUTICS, v.27, no.6, pp.522 - 529 | - |
dc.identifier.kciid | ART002519025 | - |
dc.identifier.scopusid | 2-s2.0-85070897829 | - |
dc.citation.endPage | 529 | - |
dc.citation.startPage | 522 | - |
dc.citation.title | BIOMOLECULES & THERAPEUTICS | - |
dc.citation.volume | 27 | - |
dc.citation.number | 6 | - |
dc.contributor.affiliatedAuthor | Choi, Ji Woong | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Transient middle cerebral artery occlusion (tMCAO) | - |
dc.subject.keywordAuthor | S1P(1) | - |
dc.subject.keywordAuthor | AUY954 | - |
dc.subject.keywordAuthor | M1/M2 polarization | - |
dc.subject.keywordAuthor | Microglia | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | FINGOLIMOD | - |
dc.subject.keywordPlus | MICROGLIA | - |
dc.subject.keywordPlus | SPHINGOSINE-1-PHOSPHATE | - |
dc.subject.keywordPlus | NEUROGENESIS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | STROKE | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
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.