Ketamine promotes inflammation through increasing TLR4 expression in RAW264.7 cells.
10.1007/s11596-015-1447-9
- Author:
Chen MENG
1
;
Zhen LIU
;
Gui-Lin LIU
;
Li-Sha FU
;
Min ZHANG
;
Zhao ZHANG
;
Hui-Min XIA
;
Shi-Hai ZHANG
;
You-Nian XU
Author Information
1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, 27739865@qq.com.
- Publication Type:Journal Article
- MeSH:
Anesthetics, Dissociative;
pharmacology;
Animals;
Cell Survival;
drug effects;
Gene Expression Regulation;
Inflammation Mediators;
pharmacology;
Interleukin-6;
genetics;
Ketamine;
pharmacology;
Lipopolysaccharides;
pharmacology;
Macrophages;
drug effects;
metabolism;
Male;
Mice;
N-Methylaspartate;
pharmacology;
RAW 264.7 Cells;
Signal Transduction;
drug effects;
Toll-Like Receptor 4;
genetics;
metabolism;
Tumor Necrosis Factor-alpha;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(3):419-425
- CountryChina
- Language:English
-
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.
