Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희선 | * |
dc.date.accessioned | 2018-12-07T16:30:21Z | - |
dc.date.available | 2018-12-07T16:30:21Z | - |
dc.date.issued | 2017 | * |
dc.identifier.issn | 1949-2553 | * |
dc.identifier.other | OAK-21490 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247286 | - |
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-α. 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-α processing, comp 3 additionally inhibits the expression of TNF-α. Both compounds inhibited LPS-induced activity of MAP kinases, NF-κB, 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. © Lee et al. | * |
dc.language | English | * |
dc.publisher | Impact Journals LLC | * |
dc.subject | Astrocytes | * |
dc.subject | Microglia | * |
dc.subject | MMP-8 inhibitor | * |
dc.subject | Neuroinflammation | * |
dc.subject | Systemic inflammation | * |
dc.title | Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes | * |
dc.type | Article | * |
dc.relation.issue | 45 | * |
dc.relation.volume | 8 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 78677 | * |
dc.relation.lastpage | 78690 | * |
dc.relation.journaltitle | Oncotarget | * |
dc.identifier.doi | 10.18632/oncotarget.20207 | * |
dc.identifier.wosid | WOS:000412111300041 | * |
dc.identifier.scopusid | 2-s2.0-85030454236 | * |
dc.author.google | Lee E.-J. | * |
dc.author.google | Choi M.-J. | * |
dc.author.google | Lee G. | * |
dc.author.google | Gaire B.P. | * |
dc.author.google | Choi J.W. | * |
dc.author.google | Kim H.-S. | * |
dc.contributor.scopusid | 김희선(57191372551) | * |
dc.date.modifydate | 20240118140922 | * |