Ketamine promotes inflammation through increasing TLR4 expression in RAW264.7 cells / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences)
; (6): 419-425, 2015.
Article
em En
| WPRIM
| ID: wpr-250401
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WPRO
ABSTRACT
Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.
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WPRIM
Assunto principal:
Farmacologia
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Transdução de Sinais
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Sobrevivência Celular
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Regulação da Expressão Gênica
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Lipopolissacarídeos
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N-Metilaspartato
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Interleucina-6
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Fator de Necrose Tumoral alfa
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Mediadores da Inflamação
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Receptor 4 Toll-Like
Limite:
Animals
Idioma:
En
Revista:
Journal of Huazhong University of Science and Technology (Medical Sciences)
Ano de publicação:
2015
Tipo de documento:
Article