MAO-A Inhibition by Metaxalone Reverts IL-1ß-Induced Inflammatory Phenotype in Microglial Cells.
Int J Mol Sci
; 22(16)2021 Aug 05.
Article
en En
| MEDLINE
| ID: mdl-34445126
ABSTRACT
Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1ß (IL-1ß). Control cells and IL-1ß-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1ß stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1ß also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Microglía
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Oxazolidinonas
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Interleucina-1beta
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Inflamación
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Monoaminooxidasa
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Inhibidores de la Monoaminooxidasa
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia