c-Jun N-terminal kinase and, to a lesser extent, p38 mitogen-activated protein kinase regulate inducible nitric oxide synthase expression in hyaluronan fragments-stimulated BV-2 microglia

2004 ◽  
Vol 146 (1-2) ◽  
pp. 50-62 ◽  
Author(s):  
Mei-Jen Wang ◽  
Kee-Ching G. Jeng ◽  
Jon-Son Kuo ◽  
Huan-Lian Chen ◽  
Hsin-Yi Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Midazolam Inhibits Proinflammatory Mediators in the Lipopolysaccharide-activated Macrophage

2006 ◽  
Vol 105 (1) ◽  
pp. 105-110 ◽  
Author(s):  
Seon Nyo Kim ◽  
Soo Chang Son ◽  
Sang Mook Lee ◽  
Cuk Seong Kim ◽  
Dae Goon Yoo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Mitogen Activated Protein Kinase ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
Nf Kappab ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

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.

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