|show drug details|
|Bioxyde d'azote [French]|
|Endogenous Nitrate Vasodilator|
|Endothelium-Derived Nitric Oxide|
|Nitrate Vasodilator, Endogenous|
|Nitric oxide 10% by volume or more|
|Nitric oxide, compressed [UN1660] [Poison gas]|
|Nitric oxide, compressed [UN1660] [Poison gas]|
|Nitric Oxide, Endothelium Derived|
|Nitric Oxide, Endothelium-Derived|
|Nitrogen oxide (NO)|
|Nitrosyl hydride ((NO)H)|
|Oxyde nitrique [French]|
|RCRA waste no. P076|
|RCRA waste number P076|
|Vasodilator, Endogenous Nitrate|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Inhibition of extracellular signal-regulated kinase suppresses endotoxin-induced nitric oxide synthesis in mouse macrophages and in human colon epithelial cells.. A Lahti; M Lähde; H Kankaanranta; E Moilanen (2000) The Journal of pharmacology and experimental therapeutics display abstract
Macrophages produce large amounts of nitric oxide (NO) in response to proinflammatory cytokines and lipopolysaccharide (LPS) by expressing inducible isoform of NO synthase (iNOS). We examined the role of extracellular signal-regulated kinase p42/44(MAPK) (Erk1/2) in signal transduction pathways leading to induction of NO synthesis in response to LPS in J774 mouse macrophages and T-84 human colon epithelial cells. LPS activated Erk1/2 and induced iNOS and subsequent NO production. Erk1/2 activation was inhibited by PD 98059, a specific inhibitor of mitogen-activated protein kinase kinase (Mek) that is an upstream activator of Erk1/2. At corresponding concentrations PD 98059 reduced LPS-induced NO formation by 40 to 50% by inhibiting iNOS expression in J774 and T-84 cells. Inhibition of iNOS expression was not mediated by nuclear factor-kappaB because PD 98059 had no effect on nuclear factor-kappaB activity in J774 macrophages. In addition, PD 98059 reduced LPS-induced L-arginine transport into the cells as measured in J774 macrophages, whereas the availability of tetrahydrobiopterin was not a limiting factor in NO production after PD 98059. Our results indicate that Erk1/2 activation mediates up-regulation but is not essential for LPS-induced iNOS expression.
Inhibition of p38 and ERK MAP kinases blocks endotoxin-induced nitric oxide production and differentially modulates cytokine expression.. Sang Hyun Kim; Jiyoung Kim; Raghubir P Sharma (2004) Pharmacological research : the official journal of the Italian Pharmacological Society display abstract
Mitogen-activated protein kinases (MAPKs) are thought to have a critical role in lipopolysaccharide (LPS)-induced immune responses but the molecular mechanisms underlying the mediation of these signaling are not clear. The roles of p38 and extracellular signal-regulated kinase (ERK) in the regulation of nitric oxide (NO) and proinflammatory cytokine expression in J774A.1 macrophages in response to LPS were examined. Specific inhibitors for p38 and ERK, SB203580 and PD98059, respectively, were used. LPS (30ng/ml) activated inducible nitric oxide synthase (iNOS), subsequent NO production, and gene expression for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-12. Treatment of cultures with SB203580 increased LPS-induced reactive oxygen species (ROS) production, whereas both SB203580 and PD98059 decreased LPS-induced NO production. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-1beta and IL-6. SB203580 increased LPS-induced expression of TNF-alpha and IL-12; PD98059 had no effect on these cytokines. Results indicated that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis and the expression of IL-1beta and IL-6. p38 signaling pathway is involved in LPS-induced ROS, TNF-alpha and IL-12 production.
Suppression of inflammatory arthritis by simultaneous inhibition of nitric oxide synthase and NADPH oxidase.. R Miesel; M Kurpisz; H Kroger (1996) Free radical biology & medicine display abstract
TH1-type proinflammatory cytokines induce the expression of phagocytic nitric oxide synthase (NOS) and prime the membrane-bound NADPH oxidase of neutrophils and monocytes of mice so as to attain an activated state, which upon a second stimulus releases up to 6-fold increased levels of reactive oxygen species (ROS) than do unprimed phagocytes. Enhanced levels of ROS and NO deregulate inflammatory signal transduction pathways, which play a crucial role in the pathogenesis of arthritis. The antiarthritic reactivity of diphenylene iodoniumchloride (DPI), an irreversible inhibitor of NADPH oxidase and NOS, was tested in male DBA/1xB10A(4R) hybrid mice suffering from potassium peroxochromate-induced arthritis. Daily doses of 2.8 mu mol/kg of DPI sufficed to inhibit the arthritis by 50%. A complete inhibition was obtained with 10 mu mol/kg of DPI. The reduction of overt arthritic symptoms correlated well with both the reduced levels of ROS and NO in plasma of DPI-treated mice. Our data support the hypothesis that oxidative stress and nitric oxides play a pivotal role in the pathology of arthritis, which can be therapeutically targetted by NADPH oxidase- and NO synthase-inhibitors.