J. Mcleod, H. Elford, J. Ryan
May 1, 2014
Citations
0
Influential Citations
1
Citations
Quality indicators
Journal
The Journal of Immunology
Abstract
Ribonucleotide reductase is the enzyme responsible for catalyzing the production of deoxynucleotide triphosphates (dNTPs), essential for proper DNA synthesis and cell cycle progression. Inhibitors of ribonucleotide reductase have become attractive therapeutic agents for the treatment of conditions characterized by excessive cell proliferation or inappropriate immune cell activation, including myeloproliferative disorders, psoriasis and cancer. Late phase IgE-stimulated mast cell (MC) activation elicits sustained inflammation and is marked by synthesis and secretion of cytokines that have been implicated in the inflammatory responses associated with rheumatoid arthritis, multiple sclerosis and heart disease. Given the potential utility of ribonucleotide reductase inhibitors as cytostatic agents that may influence immune cell activation, we investigated the anti-inflammatory abilities of Didox and Trimidox as a therapeutic approach to attenuate the allergic response. Our results have found that Didox and Trimidox pre-treatment yields a dose-dependent reduction in IgE-stimulated bone marrow-derived mast cells (BMMC) cytokine secretion. These effects are not directly linked to an increase in cell death. Together this preliminary data could indicate a role for Didox and Trimidox in the treatment of MC-associated inflammatory and autoimmune diseases.