A carbon monoxide-releasing molecule (CORM-3) attenuates lipopolysaccharide- and interferon-gamma-induced inflammation in microglia.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 0
Abstract
The development of carbon monoxide-releasing molecules (CO-RMs) in recent years helped to shed more light on the diverse range of anti-inflammatory and cytoprotective activities of CO gas. In this study, we examined the effect of a ruthenium-based water-soluble CO carrier (CORM-3) on lipopolysaccharide (LPS)- and interferon-gamma (INF-gamma)-induced inflammatory responses in BV-2 microglial cells and explored the possible mechanisms of action. BV-2 microglial cells were stimulated with either LPS or INF-gamma in the presence of CORM-3 and the inflammatory response evaluated by assessing the effect on nitric oxide production (nitrite levels) and tumor necrosis factor-alpha (TNF-alpha) release. Similar experiments were also performed in the presence of inhibitors of guanylate cyclase (ODQ), NO synthase (L-NAME), heme oxygenase activity (tin protoporphyrin IX) or various mitogen-activated protein kinase (MAPK) inhibitors. CORM-3 significantly attenuated the inflammatory response to LPS and INF-gamma as evidenced by a significant reduction (p < 0.001) in nitrite levels and TNF-alpha production (P < 0.05). Such effect was maintained in the presence of ODQ, L-NAME or tin protoporphyrin without showing any cytotoxicity. The use of an inactive form of CORM-3 that does not contain carbonyl groups (Ru(DMSO)(4)Cl(2) failed to inhibit the increase in inflammatory markers suggesting that liberated CO mediates the observed effects. In addition, inhibition of phosphatidylinositol-3-phosphate kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways seemed to amplify the anti-inflammatory effect of CORM-3, particularly in cells stimulated with INF-gamma. These results suggest that the anti-inflammatory action of CORM-3 could be exploited to mitigate microglia activation in neuro-inflammatory diseases.
Authors and Affiliations
Mohamed Bani-Hani, David Greenstein, Brian Mann, Colin Green, Roberto Motterlini
Keywords
Related Articles
- EP ID EP144413
- DOI -
- Views 98
- Downloads 0
Aldosterone augments LOX-1-mediated low-density lipoprotein uptake in human umbilical artery endothelial cells.
Aldosterone and oxidized low-density lipoprotein (oxLDL) are recognized risk factors for cardiovascular disease and atherosclerosis. LOX-1 is a multi-ligand receptor originally identified as the endothelial oxLDL recepto...
Disparate effects of anti-TNF-α therapies on measures of disease activity and mediators of endothelial damage in ankylosing spondylitis.
Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethyl...
Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction.
Background: Contact hypersensitivity (CS) reaction in the skin is T-cell mediated immune reaction which plays a major role in the pathogenesis and chronicity of various inflammatory skin disorders and, like other delayed...
Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats.
Increasing evidence shows that serotonin (5-hydroxytryptamine - 5-HT) plays a modulatory role in memory functions. 5-HT transmission has been implicated in learning and memory. Both 5-HT depletion and specific 5-HT agoni...
Transcellular biosynthesis of eicosanoids.
The metabolism of arachidonic acid into biologically active compounds involves the sequential activity of a number of enzymes, sometimes showing a unique expression profile in different cells. The main metabolic pathways...