Midazolam suppresses interleukin-1β-induced interleukin-6 release from rat glial cells

<p>Abstract</p> <p>Background</p> <p>Peripheral-type benzodiazepine receptor (PBR) expression levels are low in normal human brain, but their levels increase in inflammation, brain injury, neurodegenerative states and gliomas. It has been reported that PBR functions as an immunomodulator. The mechanisms of action of midazolam, a benzodiazepine, in the immune system in the CNS remain to be fully elucidated. We previously reported that interleukin (IL)-1β stimulates IL-6 synthesis from rat C6 glioma cells and that IL-1β induces phosphorylation of inhibitory kappa B (IκB), p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-<it>Jun </it>N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription (STAT)3. It has been shown that p38 MAP kinase is involved in IL-1β-induced IL-6 release from these cells. In the present study, we investigated the effect of midazolam on IL-1β-induced IL-6 release from C6 cells, and the mechanisms of this effect.</p> <p>Methods</p> <p>Cultured C6 cells were stimulated by IL-1β. IL-6 release from C6 cells was measured using an enzyme-linked immunosorbent assay, and phosphorylation of IκB, the MAP kinase superfamily, and STAT3 was analyzed by Western blotting.</p> <p>Results</p> <p>Midazolam, but not propofol, inhibited IL-1β-stimulated IL-6 release from C6 cells. The IL-1β-stimulated levels of IL-6 were suppressed by wedelolactone (an inhibitor of IκB kinase), SP600125 (an inhibitor of SAPK/JNK), and JAK inhibitor I (an inhibitor of JAK 1, 2 and 3). However, IL-6 levels were not affected by PD98059 (an inhibitor of MEK1/2). Midazolam markedly suppressed IL-1β-stimulated STAT3 phosphorylation without affecting the phosphorylation of p38 MAP kinase, SAPK/JNK or IκB.</p> <p>Conclusion</p> <p>These results strongly suggest that midazolam inhibits IL-1β-induced IL-6 release in rat C6 glioma cells via suppression of STAT3 activation. Midazolam may affect immune system function in the CNS.</p

Gosha-jinki-gan Reduces Transmitter Proteins and Sensory Receptors Associated with C Fiber Activation Induced by Acetic Acid in Rat Urinary Bladder

This is a preprint of an article published in [NEUROUROLOGY AND URODYNAMICS. 27(8):832-837 (2008)].ArticleNEUROUROLOGY AND URODYNAMICS. 27(8):832-837 (2008)journal articl

Performance Evaluation of Hydrogen Permeability of Pore-filling Membrane Prepared from Nanoparticles

ナノダイナミクス国際シンポジウム 平成22年1月21日(木) 於長崎大学Nagasaki Symposium on Nano-Dynamics 2010 (NSND2010), January 21, 2010, Nagasaki University, Nagasaki, Japan, Invited Lectur

Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

<p>Abstract</p> <p>Background</p> <p>Hydrogen (H₂), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. Therefore, we investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in the metabolic syndrome rat model, SHR.Cg-<it>Lepr^cp</it>/NDmcr (SHR-cp).</p> <p>Methods</p> <p>Male SHR-cp rats (5 weeks old) were divided into 2 groups: an HRW group was given oral HRW for 16 weeks, and a control group was given distilled water. At the end of the experiment, each rat was placed in a metabolic cage for 24 h, fasted for 12 h, and anesthetized; the blood and kidneys were then collected.</p> <p>Results</p> <p>Sixteen weeks after HRW administration, the water intake and urine flow measured in the metabolic cages were significantly higher in the HRW group than in the control group. The urinary ratio of albumin to creatinine was significantly lower and creatinine clearance was higher in the HRW group than in the control group. After the 12-h fast, plasma urea nitrogen and creatinine in the HRW group were significantly lower than in the control group. The plasma total antioxidant capacity was significantly higher in the HRW group than in the control group. The glomerulosclerosis score for the HRW group was significantly lower than in the control group, and a significantly positive correlation was observed between this score and plasma urea nitrogen levels.</p> <p>Conclusion</p> <p>The present findings suggest that HRW conferred significant benefits against abnormalities in the metabolic syndrome model rats, at least by preventing and ameliorating glomerulosclerosis and creatinine clearance.</p

Activation of protein phosphatase 2A by cAMP-dependent protein kinase-catalyzed phosphorylation of the 74-kDa B″ (δ) regulatory subunit in vitro and identification of the phosphorylation sites

AbstractHuman erythrocyte protein phosphatase 2A, which comprises a 34-kDa catalytic C subunit, a 63-kDa regulatory A subunit and a 74-kDa regulatory B″ (δ) subunit, was phosphorylated at serine residues of B″ in vitro by cAMP-dependent protein kinase (A-kinase). In the presence and absence of 0.5 μM okadaic acid (OA), A-kinase gave maximal incorporation of 1.7 and 1.0 mol of phosphate per mol of B″, respectively. The Km value of A-kinase for CAB″ was 0.17±0.01 μM in the presence of OA. The major in vitro phosphorylation sites of B″ were identified as Ser-60, -75 and -573 in the presence of OA, and Ser-75 and -573 in the absence of OA. Phosphorylation of B″ did not dissociate B″ from CA, and stimulated the molecular activity of CAB″ toward phosphorylated H1 and H2B histones, 3.8- and 1.4-fold, respectively, but not toward phosphorylase a