Matrix Metalloproteinase-8 Plays a Pivotal Role in Neuroinflammation by Modulating TNF-alpha Activation
DC Field | Value | Language |
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dc.contributor.author | Lee, Eun-Jung | - |
dc.contributor.author | Han, Jeong Eun | - |
dc.contributor.author | Woo, Moon-Sook | - |
dc.contributor.author | Shin, Jin A. | - |
dc.contributor.author | Park, Eun-Mi | - |
dc.contributor.author | Kang, Jihee Lee | - |
dc.contributor.author | Moon, Pyong Gon | - |
dc.contributor.author | Baek, Moon-Chang | - |
dc.contributor.author | Son, Woo-Sung | - |
dc.contributor.author | Ko, Young Tag | - |
dc.contributor.author | Choi, Ji Woong | - |
dc.contributor.author | Kim, Hee-Sun | - |
dc.date.available | 2020-02-28T16:43:21Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2014-09-01 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12306 | - |
dc.description.abstract | Matrix metalloproteinases (MMPs) play important roles in normal brain development and synaptic plasticity, although aberrant expression of MMPs leads to brain damage, including blood-brain barrier disruption, inflammation, demyelination, and neuronal cell death. In this article, we report that MMP-8 is upregulated in LPS-stimulated BV2 microglial cells and primary cultured microglia, and treatment of MMP-8 inhibitor (M8I) or MMP-8 short hairpin RNA suppresses proinflammatory molecules, particularly TNF-alpha secretion. Subsequent experiments showed that MMP-8 exhibits TNF-alpha-converting enzyme (TACE) activity by cleaving the prodomain of TNF-alpha (A(74)/Q(75), A(76)/V-77 residues) and, furthermore, that M8I inhibits TACE activity more efficiently than TAPI-0, a general TACE inhibitor. Biochemical analysis of the underlying anti-inflammatory mechanisms of M8I revealed that it inhibits MAPK phosphorylation, NE-kappa B/AP-1 activity, and reactive oxygen species production. Further support for the proinflammatory role of microglial MMP-8 was obtained from an in vivo animal model of neuroinflammatory disorder. MMP-8 is upregulated in septic conditions, particularly in microglia. Administration of M8I or MMP-8 short hairpin RNA significantly inhibits microglial activation and expression/secretion of TNF-alpha in brain tissue, serum, and cerebrospinal fluid of LPS-induced septic mice. These results demonstrate that MMP-8 critically mediates microglial activation by modulating TNF-alpha activity, which may explain neuroinflammation in septic mouse brain. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.subject | NECROSIS-FACTOR-ALPHA | - |
dc.subject | RAT-BRAIN | - |
dc.subject | NEURODEGENERATIVE DISEASES | - |
dc.subject | INFLAMMATORY DISORDERS | - |
dc.subject | SIGNALING PATHWAYS | - |
dc.subject | CONVERTING-ENZYME | - |
dc.subject | MICROGLIAL CELLS | - |
dc.subject | NERVOUS-SYSTEM | - |
dc.subject | NADPH OXIDASES | - |
dc.subject | INHIBITION | - |
dc.title | Matrix Metalloproteinase-8 Plays a Pivotal Role in Neuroinflammation by Modulating TNF-alpha Activation | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000341140600040 | - |
dc.identifier.doi | 10.4049/jimmunol.1303240 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.193, no.5, pp.2384 - 2393 | - |
dc.identifier.scopusid | 2-s2.0-84907021020 | - |
dc.citation.endPage | 2393 | - |
dc.citation.startPage | 2384 | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 193 | - |
dc.citation.number | 5 | - |
dc.contributor.affiliatedAuthor | Han, Jeong Eun | - |
dc.contributor.affiliatedAuthor | Ko, Young Tag | - |
dc.contributor.affiliatedAuthor | Choi, Ji Woong | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | RAT-BRAIN | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | INFLAMMATORY DISORDERS | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | CONVERTING-ENZYME | - |
dc.subject.keywordPlus | MICROGLIAL CELLS | - |
dc.subject.keywordPlus | NERVOUS-SYSTEM | - |
dc.subject.keywordPlus | NADPH OXIDASES | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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