Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Kim, Jieun | - |
dc.contributor.author | Park, Jin-Hee | - |
dc.contributor.author | Shah, Keshvi | - |
dc.contributor.author | Mitchell, Scott John | - |
dc.contributor.author | Cho, Kwangwook | - |
dc.contributor.author | Hoe, Hyang-Sook | - |
dc.date.accessioned | 2021-12-02T14:00:17Z | - |
dc.date.available | 2021-12-02T14:00:17Z | - |
dc.date.created | 2021-11-25 | - |
dc.date.issued | 2021-10 | - |
dc.identifier.issn | 1663-4365 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/15893 | - |
dc.description.abstract | The sulfonylurea drug gliquidone is FDA approved for the treatment of type 2 diabetes. Binding of gliquidone to ATP-sensitive potassium channels (SUR1, Kir6 subunit) in pancreatic β-cells increases insulin release to regulate blood glucose levels. Diabetes has been associated with increased levels of neuroinflammation, and therefore the potential effects of gliquidone on micro- and astroglial neuroinflammatory responses in the brain are of interest. Here, we found that gliquidone suppressed LPS-mediated microgliosis, microglial hypertrophy, and proinflammatory cytokine COX-2 and IL-6 levels in wild-type mice, with smaller effects on astrogliosis. Importantly, gliquidone downregulated the LPS-induced microglial NLRP3 inflammasome and peripheral inflammation in wild-type mice. An investigation of the molecular mechanism of the effects of gliquidone on LPS-stimulated proinflammatory responses showed that in BV2 microglial cells, gliquidone significantly decreased LPS-induced proinflammatory cytokine levels and inhibited ERK/STAT3/NF-κB phosphorylation by altering NLRP3 inflammasome activation. In primary astrocytes, gliquidone selectively affected LPS-mediated proinflammatory cytokine expression and decreased STAT3/NF-κB signaling in an NLRP3-independent manner. These results indicate that gliquidone differentially modulates LPS-induced microglial and astroglial neuroinflammation in BV2 microglial cells, primary astrocytes, and a model of neuroinflammatory disease. Copyright © 2021 Kim, Park, Shah, Mitchell, Cho and Hoe. | - |
dc.language | English | - |
dc.publisher | Frontiers Media S.A. | - |
dc.title | The Anti-diabetic Drug Gliquidone Modulates Lipopolysaccharide-Mediated Microglial Neuroinflammatory Responses by Inhibiting the NLRP3 Inflammasome | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fnagi.2021.754123 | - |
dc.identifier.scopusid | 2-s2.0-85119078967 | - |
dc.identifier.bibliographicCitation | Frontiers in Aging Neuroscience, v.13 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordAuthor | gliquidone | - |
dc.subject.keywordAuthor | LPS (lipopolysaccharide) | - |
dc.subject.keywordAuthor | microgliosis | - |
dc.subject.keywordAuthor | neuroinflammation | - |
dc.subject.keywordAuthor | NLRP3 inflammasome | - |
dc.subject.keywordAuthor | proinflammatory cytokine | - |
dc.subject.keywordPlus | K-ATP CHANNELS | - |
dc.subject.keywordPlus | SENSITIVE POTASSIUM CHANNELS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | GLIBENCLAMIDE | - |
dc.subject.keywordPlus | EFFLUX | - |
dc.subject.keywordPlus | CA2+ | - |
dc.subject.keywordPlus | SULFONYLUREAS | - |
dc.subject.keywordPlus | CYTOKINES | - |
dc.subject.keywordPlus | ISCHEMIA | - |
dc.subject.keywordPlus | AGONISTS | - |
dc.citation.title | Frontiers in Aging Neuroscience | - |
dc.citation.volume | 13 | - |