https://scholars.lib.ntu.edu.tw/handle/123456789/519109
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Mohanraj M. | en_US |
dc.contributor.author | Sekar P. | en_US |
dc.contributor.author | HORNG-HUEI LIOU | en_US |
dc.contributor.author | Chang S.-F. | en_US |
dc.contributor.author | WAN-WAN LIN | en_US |
dc.creator | Mohanraj M.;Sekar P.;Horng-Huei Liou;Chang S.-F.;Lin W.-W. | - |
dc.date.accessioned | 2020-11-03T09:53:15Z | - |
dc.date.available | 2020-11-03T09:53:15Z | - |
dc.date.issued | 2019 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048045061&doi=10.1007%2fs12035-018-1135-4&partnerID=40&md5=2127dfe2d3eaab9178589944fc2ac828 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/519109 | - |
dc.description.abstract | Microglial activation has long been recognized as a hallmark of neuroinflammation. Recently, the bacillus Calmette-Guerin (BCG) vaccine has been reported to exert neuroprotective effects against several neurodegenerative disorders. Trehalose-6,6′-dibehenate (TDB) is a synthetic analogue of trehalose-6,6′-dimycolate (TDM, also known as the mycobacterial cord factor) and is a new adjuvant of tuberculosis subunit vaccine currently in clinical trials. Both TDM and TDB can activate macrophages and dendritic cells through binding to C-type lectin receptor Mincle; however, its action mechanism in microglia and their relationship with neuroinflammation are still unknown. In this article, we found that TDB inhibited LPS-induced M1 microglial polarization in primary microglia and BV-2 cells. However, TDB itself had no effects on IKK, p38, and JNK activities or cytokine expression. In contrast, TDB activated ERK1/2 through PLC-γ1/PKC signaling and in turn decreased LPS-induced NF-κB nuclear translocation. Furthermore, TDB-induced AMPK activation via PLC-γ1/calcium/CaMKKβ-dependent pathway and thereby enhanced M2 gene expressions. Interestingly, knocking out Mincle did not alter the anti-inflammatory and M2 polarization effects of TDB in microglia. Conditional media from LPS-stimulated microglial cells can induce in vitro neurotoxicity, and this action was attenuated by TDB. Using a mouse neuroinflammation model, we found that TDB suppressed LPS-induced M1 microglial activation and sickness behavior, but promoted M2 microglial polarization in both WT and Mincle ?/? mice. Taken together, our results suggest that TDB can act independently of Mincle to inhibit LPS-induced inflammatory response through PLC-γ1/PKC/ERK signaling and promote microglial polarization towards M2 phenotype via PLC-γ1/calcium/CaMKKβ/AMPK pathway. Thus, TDB may be a promising therapeutic agent for the treatment of neuroinflammatory diseases. ? 2018, Springer Science+Business Media, LLC, part of Springer Nature. | - |
dc.publisher | Humana Press Inc. | - |
dc.relation.ispartof | Molecular Neurobiology | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | antiinflammatory agent; immunoglobulin enhancer binding protein; lipopolysaccharide; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; phospholipase C gamma1; protein kinase C; trehalose 6,6' dibehenate; unclassified drug; antiinflammatory agent; glycolipid; lipopolysaccharide; mitogen activated protein kinase; phospholipase C; protein kinase C; trehalose 6,6'-dibehenate; animal cell; animal experiment; animal model; antiinflammatory activity; Article; BV-2 cell line; controlled study; enzyme activation; gene expression; human; human cell; in vitro study; in vivo study; male; MAPK signaling; microglia; mouse; nervous system inflammation; neuroprotection; neurotoxicity; nonhuman; polarization; protein expression; animal; animal behavior; brain; cell line; cell polarity; drug effect; inflammation; metabolism; microglia; signal transduction; Animals; Anti-Inflammatory Agents; Behavior, Animal; Brain; Cell Line; Cell Polarity; Extracellular Signal-Regulated MAP Kinases; Glycolipids; Inflammation; Lipopolysaccharides; Mice; Microglia; Protein Kinase C; Signal Transduction; Type C Phospholipases | - |
dc.title | The Mycobacterial Adjuvant Analogue TDB Attenuates Neuroinflammation via Mincle-Independent PLC-γ1/PKC/ERK Signaling and Microglial Polarization | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1007/s12035-018-1135-4 | - |
dc.identifier.pmid | 29876879 | - |
dc.identifier.scopus | 2-s2.0-85048045061 | - |
dc.relation.pages | 1167-1187 | - |
dc.relation.journalvolume | 56 | - |
dc.relation.journalissue | 2 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | National Taiwan University Hospital Yun-Lin Branch | - |
crisitem.author.dept | Neurology | - |
crisitem.author.dept | Pharmacology | - |
crisitem.author.dept | Brain and Mind Sciences | - |
crisitem.author.dept | Neurology-NTUH | - |
crisitem.author.dept | Pharmacology | - |
crisitem.author.orcid | 0000-0001-6537-5346 | - |
crisitem.author.orcid | 0000-0002-3207-734X | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系 |
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