Neuraminidase inhibitors reduce nitric oxide production in influenza virus-infected and gamma interferon-activated RAW 264.7 macrophages.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 6
Abstract
The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by macrophages, which abundantly generate a free radical, nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors (NIs) restrict influenza virus replication but whether they can suppress NO production within macrophages is unknown. RAW 264.7 macrophages were exposed to interferon-gamma (IFN-gamma), live influenza (A/PR/8/34) or a combination of both and were treated with NIs (oseltamivir or zanamivir). Results revealed that the drugs reduced a synergy between influenza and IFN-gamma in NO synthesis within the cells at all of the used concentrations (0.01, 0.1, 1 mug/ml). In contrast to zanamivir, this effect occurred in a concentration-dependent manner with oseltamivir treatment. On the other hand, all concentrations of zanamivir significantly suppressed NO production in comparison to that upon the combined exposure only (p < 0.05). Both compounds also considerably decreased NO generation in the IFN-gamma-stimulated macrophages, and zanamivir in the influenza-infected cells as well. However, neither of the drugs inhibited iNOS mRNAexpression in the cells containing these stimulants. Additionally, the data indicate that a prodrug oseltamivir can be activated in vitro within the macrophage cultures. These findings are important for designing treatment approaches to limit pulmonary inflammation during influenza infection.
Authors and Affiliations
Tomas Kacergius, Arvydas Ambrozaitis, Yuping Deng, Stefan Gravenstein
Keywords
Related Articles
- EP ID EP112848
- DOI -
- Views 98
- Downloads 0
9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease.
In a previous study, a primary culture of midbrain cells was exposed to 9-methyl-beta-carboline for 48 h, which caused an increase in the number of tyrosine hydroxylase-positive cells. Quantitative RT-PCR revealed increa...
Evaluation of the antioxidative properties of lipoxygenase inhibitors.
Background: Oxidative stress is a component of many pathological conditions including neurodegenerative diseases and inflammation. An important source of reactive oxygen species (ROS) are lipoxygenases (LOX) - enzymes re...
Role of the SOCS in monocytes/macrophages-related pathologies. Are we getting closer to a new pharmacological target?
The suppressors of cytokine signalling (SOCS) are proteins that restrict the functions of cytokines. Since their discovery, the state of knowledge regarding the SOCS is being regularly updated. One of the aspects of thei...
Liver X receptor (LXR) and the reproductive system--a potential novel target for therapeutic intervention.
Liver X receptor (LXR) alpha and beta are ligand-activated transcription factors that regulate the expression of genes involved in the removal of cholesterol from cells by high-density lipoproteins, the transport of chol...
677C > T and 1298A > C MTHFR polymorphisms affect arechin treatment outcome in rheumatoid arthritis.
Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), arechin (hydroxychloroquine) remains the mainstay because of both cost-effectiveness and experience with its use. However, th...