Linked Life Data

9473138

Source:http://linkedlifedata.com/resource/pubmed/id/9473138

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1998-3-26
pubmed:abstractText
The level of intracellular cyclic nucleotides is a regulatory factor in a variety of immune processes. Increases in intracellular cyclic AMP (cAMP) and/or cyclic GMP (cGMP) concentration by the inhibition of phosphodiesterase have been shown to modulate the inflammatory response. Amrinone is a clinically used positive inotropic agent which elevates intracellular cAMP and cGMP levels by selective inhibition of the phosphodiesterase III isoenzyme. In the current study, we investigated the effect of various concentrations (1-300 microM) of amrinone on lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and of nitric oxide (NO) in vitro. In cultured murine J774.1 macrophages, 1 ng/ml-10 microg/ml of lipopolysaccharide from Escherichia coli O55:B5 induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and nitrite (breakdown product of NO). Pretreatment of cells with amrinone caused a dose-dependent suppression of TNF-alpha production in the concentration range of 1-100 microM. Furthermore, this drug suppressed NO production in the range of 30-300 microM. Similarly to the results in the J774.1 cells, amrinone also inhibited TNF-alpha and NO production in the range of 10-100 microM in primary rat peritoneal macrophages. At 300 microM, but not at lower concentrations, amrinone inhibited interleukin-10 production in lipopolysaccharide-treated J774.1 macrophages. Pretreatment of the macrophages with 100 and 300 microM amrinone increased the lipopolysaccharide-elicited translocation of nuclear factor-kappa B. Taken together, our results indicate that the phosphodiesterase III inhibitor amrinone modulates the activation/production of many pro- and anti-inflammatory factors in endotoxin-stimulated cells. It remains to be further investigated how such immunomodulatory effects contribute to the clinical profile of the agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
215-21
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9473138-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:9473138-Amrinone, pubmed-meshheading:9473138-Animals, pubmed-meshheading:9473138-Cell Culture Techniques, pubmed-meshheading:9473138-Cyclic Nucleotide Phosphodiesterases, Type 3, pubmed-meshheading:9473138-Interleukin-10, pubmed-meshheading:9473138-Lipopolysaccharides, pubmed-meshheading:9473138-Macrophage Activation, pubmed-meshheading:9473138-Macrophages, pubmed-meshheading:9473138-Male, pubmed-meshheading:9473138-Mice, pubmed-meshheading:9473138-Monocytes, pubmed-meshheading:9473138-Nitric Oxide, pubmed-meshheading:9473138-Nitrites, pubmed-meshheading:9473138-Phosphodiesterase Inhibitors, pubmed-meshheading:9473138-Rats, pubmed-meshheading:9473138-Rats, Wistar, pubmed-meshheading:9473138-Tumor Necrosis Factor-alpha
pubmed:year
1997
pubmed:articleTitle
Effect of the phosphodiesterase III inhibitor amrinone on cytokine and nitric oxide production in immunostimulated J774.1 macrophages.
pubmed:affiliation
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't