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Published on: May 31, 2018
Midazolam inhibits proinflammatory mediators in the lipopolysaccharide-activated macrophage
Seon Nyo Kim1, Soo Chang Son, Sang Mook Lee
1Department of Physiology, Chungnam National University, Daejeon, Korea.
Background:
Midazolam, a benzodiazepine, has a hypnotic effect and is widely used as a sedative. The role of midazolam in activation of macrophages during sepsis is not known. The aim of this study was to evaluate the antiinflammatory actions of midazolam in cultured macrophages.
Methods:
Using a macrophage cell line, RAW264.7 cells, the effect of midazolam on proinflammatory mediators and activation of mitogen-activated protein kinase was measured by Western blot. Nuclear factor-kappaB (NF-kappaB) activation and translocation of p65 subunit of NF-kappaB was measured using luciferase assay and immunocytochemistry. Superoxide production was measured by lucigenin chemiluminescence.
Results:
Midazolam significantly inhibited lipopolysaccharide-induced up-regulation of both cyclooxygenase 2 and inducible nitric oxide synthase in a dose-dependent manner (approximately 3-30 microm). IkappaB-alpha degradation and NF-kappaB transcriptional activity induced by lipopolysaccharide were also suppressed by the midazolam. Nuclear translocation of the p65 subunit of NF-kappaB was inhibited by midazolam. Furthermore, midazolam suppressed phosphorylation of p38 mitogen-activated protein kinase and also inhibited lipopolysaccharide-induced superoxide production in macrophages.
Conclusions:
These results suggest that midazolam has an antiinflammatory action by inhibiting inducible nitric oxide synthase and cyclooxygenase-2 expression, possibly through suppression of NF-kappaB and p38 mitogen-activated protein kinase activation.
Insights
Midazolam, a sedative, demonstrates anti-inflammatory effects by inhibiting key inflammatory pathways in macrophages. This study reveals its potential to suppress sepsis-related inflammation by reducing nitric oxide synthase and cyclooxygenase-2.
Area of Science:
- Immunology
- Pharmacology
Background:
- Midazolam is a widely used benzodiazepine sedative.
- Its role in macrophage activation during sepsis is unknown.
- This study investigates midazolam's anti-inflammatory actions in macrophages.
Purpose of the Study:
- To evaluate the anti-inflammatory effects of midazolam.
- To determine midazolam's impact on macrophage activation pathways.
Main Methods:
- Utilized RAW264.7 macrophage cell line.
- Measured proinflammatory mediators and mitogen-activated protein kinase activation via Western blot.
- Assessed nuclear factor-kappaB (NF-kappaB) activation, p65 translocation, and superoxide production.
Main Results:
- Midazolam dose-dependently inhibited lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase.
- Suppressed IkappaB-alpha degradation, NF-kappaB transcriptional activity, and p65 nuclear translocation.
- Inhibited p38 mitogen-activated protein kinase phosphorylation and macrophage superoxide production.
Conclusions:
- Midazolam exhibits anti-inflammatory properties.
- It inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression.
- Suppression of NF-kappaB and p38 mitogen-activated protein kinase activation mediates these effects.
