Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 이지희 | * |
dc.contributor.author | 김희선 | * |
dc.contributor.author | 박진선 | * |
dc.contributor.author | 이은정 | * |
dc.date.accessioned | 2019-01-02T16:30:15Z | - |
dc.date.available | 2019-01-02T16:30:15Z | - |
dc.date.issued | 2018 | * |
dc.identifier.issn | 1742-2094 | * |
dc.identifier.other | OAK-24029 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/248069 | - |
dc.description.abstract | BackgroundRecent evidence suggests that reactive astrocytes play an important role in neuroinflammation and neurodegenerative diseases. Thus, controlling astrocyte reactivity has been suggested as a promising strategy for treating neurodegenerative diseases. In the present study, we investigated whether a matrix metalloproteinase (MMP)-8 inhibitor, M8I, could control neuroinflammation in lipoteichoic acid (LTA)-stimulated rat primary astrocytes.MethodsThe effects of M8I on the expression of inducible nitric oxide synthase, cytokines, and MMPs were examined in LTA-stimulated rat primary astrocytes by ELISA, RT-PCR, and Western blot analysis. The effects of M8I on reactive oxygen species (ROS) generation and phase II antioxidant enzyme expression were examined by the DCF-DA assay, RT-PCR, and Western blot analysis. The detailed molecular mechanisms underlying the anti-inflammatory and antioxidant effects of M8I were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, Western blot, and RT-PCR analysis.ResultsTreatment with LTA, a major cell wall component of Gram-positive bacteria, led to astrocyte activation and induced the expression of inflammatory molecules such as iNOS, COX-2, and pro-inflammatory cytokines. In addition, LTA induced the expression of MMPs such as MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 in rat primary astrocytes. Based on previous reports showing that MMP-8 plays a role as a proinflammatory mediator in microglia, we investigated whether MMP-8 is also involved in inflammatory reactions of reactive astrocytes. We found that treatment of astrocytes with M8I significantly inhibited LTA-induced expression of iNOS, TNF-, IL-1, IL-6, and TLR-2. In addition, M8I inhibited LTA-induced NF-B, MAP kinase, and Akt activities, while it increased the anti-inflammatory PPAR- activities. Moreover, M8I showed antioxidant effects by suppressing ROS production in LTA- or H2O2-stimulated astrocytes. Interestingly, M8I increased the expression of phase II antioxidant enzymes such as hemeoxygenase-1, NQO1, catalase, and MnSOD by modulating the Nrf2/ARE signaling pathway.ConclusionsThe data collectively suggest the therapeutic potential of an MMP-8 inhibitor in neuroinflammatory disorders that are associated with astrocyte reactivity. | * |
dc.language | English | * |
dc.publisher | BMC | * |
dc.subject | MMP-8 inhibitor | * |
dc.subject | Astrocytes | * |
dc.subject | Neuroinflammation | * |
dc.subject | Anti-inflammatory | * |
dc.subject | Antioxidant | * |
dc.subject | Molecular mechanisms | * |
dc.title | Anti-inflammatory and anti-oxidant mechanisms of an MMP-8 inhibitor in lipoteichoic acid-stimulated rat primary astrocytes: involvement of NF-B, Nrf2, and PPAR- signaling pathways | * |
dc.type | Article | * |
dc.relation.volume | 15 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | JOURNAL OF NEUROINFLAMMATION | * |
dc.identifier.doi | 10.1186/s12974-018-1363-6 | * |
dc.identifier.wosid | WOS:000451050900001 | * |
dc.author.google | Lee, Eun-Jung | * |
dc.author.google | Park, Jin-Sun | * |
dc.author.google | Lee, Yu-Young | * |
dc.author.google | Kim, Do-Yeon | * |
dc.author.google | Kang, Jihee Lee | * |
dc.author.google | Kim, Hee-Sun | * |
dc.contributor.scopusid | 이지희(7404517577) | * |
dc.contributor.scopusid | 김희선(57191372551) | * |
dc.contributor.scopusid | 박진선(54914743600) | * |
dc.contributor.scopusid | 이은정(57212665881) | * |
dc.date.modifydate | 20240215165648 | * |