Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes
DC Field | Value | Language |
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dc.contributor.author | Lee, Eun-Jung | - |
dc.contributor.author | Choi, Min-Ji | - |
dc.contributor.author | Lee, Gyeongjin | - |
dc.contributor.author | Gaire, Bhakta Prasad | - |
dc.contributor.author | Choi, Ji Woong | - |
dc.contributor.author | Kim, Hee-Sun | - |
dc.date.available | 2020-02-27T16:44:05Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-10-03 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5585 | - |
dc.description.abstract | Matrix metalloproteinases (MMPs) play a pivotal role in neuroinflammation that is associated with neurodegenerative diseases. Our group recently reported that MMP-8 mediates inflammatory reactions by modulating the processing of TNF-alpha. To improve the efficacy of the currently available MMP-8 inhibitor (M8I), we have synthesized structurally modified M8I derivatives (comp 2, 3, 4, 5) and compared their efficacy with original compound (comp 1). Among M8I derivatives, comp 2, 3, and 5 inhibited the production of NO, ROS, and IL-6 more efficiently than the original compound in lipopolysaccharide (LPS)-stimulated microglia. When we compared the anti-inflammatory mechanisms of the most effective derivative, comp 3, with comp 1, comp 3 suppressed the mRNA expression of iNOS and cytokines more efficiently than comp 1. Although comp 1 inhibits only TNF-alpha processing, comp 3 additionally inhibits the expression of TNF-alpha. Both compounds inhibited LPS-induced activity of MAP kinases, NF-kappa B, and AP-1, while they increased heme oxygenase-1 expression by upregulating AMPK-Nrf2 signaling. Overall, the effect of comp 3 on anti-inflammatory signaling was much stronger than comp 1. We verified the anti-inflammatory effects of comp 1 and 3 in the LPS-injected mouse brain and primary cultured astrocytes. Comp 1 and 3 suppressed microglial activation, astrogliosis, and proinflammatory gene expression in the brain. Moreover, the compounds inhibited proinflammatory gene expression in the cultured astrocytes. Collectively, our data suggest that the MMP-8 inhibitor may be a promising therapeutic agent for neuroinflammatory disorders. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.subject | PROTEIN-KINASE | - |
dc.subject | CEREBRAL-ISCHEMIA | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | EXPRESSION | - |
dc.subject | CELLS | - |
dc.subject | AMPK | - |
dc.subject | POLARIZATION | - |
dc.subject | INFLAMMATION | - |
dc.subject | DISORDERS | - |
dc.subject | MECHANISM | - |
dc.title | Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000412111300041 | - |
dc.identifier.doi | 10.18632/oncotarget.20207 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.8, no.45, pp.78677 - 78690 | - |
dc.identifier.scopusid | 2-s2.0-85030454236 | - |
dc.citation.endPage | 78690 | - |
dc.citation.startPage | 78677 | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 8 | - |
dc.citation.number | 45 | - |
dc.contributor.affiliatedAuthor | Gaire, Bhakta Prasad | - |
dc.contributor.affiliatedAuthor | Choi, Ji Woong | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | MMP-8 inhibitor | - |
dc.subject.keywordAuthor | neuroinflammation | - |
dc.subject.keywordAuthor | microglia | - |
dc.subject.keywordAuthor | astrocytes | - |
dc.subject.keywordAuthor | systemic inflammation | - |
dc.subject.keywordPlus | PROTEIN-KINASE | - |
dc.subject.keywordPlus | CEREBRAL-ISCHEMIA | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | AMPK | - |
dc.subject.keywordPlus | POLARIZATION | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | DISORDERS | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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