PREVENTIVE, THERAPEUTIC, AND ETHICAL APPROACH IN PRECLINICAL AND CLINICAL STUDIES OF THE GENES AND MODULATORS OF REDOX CELL SIGNALING IN IMMUNE, INFLAMMATORY AND PROLIFERATIVE CELL RESPONSE

Cell signalling mediated by oxidative stress, a redox-dependent and NF-?B sensitive phenomenon, has a marked effect upon proliferation, differentiation, and apoptosis. ROS mediate proinflammatory/proliferative/degenerative processes in cancerogenesis, diabetes, atherosclerosis, aging, neurodegenerative diseases, rheumatoid arthritis, sarcoidosis, renal insufficiency. Dysregulation of cellular signalling pathways in these diseases seems to occur following the same pattern: redox status dysbalance, altered expression of the genes coding TNF-? and TNF-RII, IFNg, PPARs, TLRs, DDAH disturbed metabolism of arginine, polyamines and NO synthesis, MMP activation. Redox modification of transcription factors and products of gene expression, responsible for regulation of the processes of inflammation/proliferation, and cancerogenesis, alters their affinity for responsive element in a gene, creates new protein-protein interactions, lead to their conformational abnormality. Interactions of target gene products and types of epigenetic changes are the key to understanding molecular mechanisms of chronic inflammation, immune response and proliferation. These processes together lead to an unstable genome, and initiation of cancerogenesis. Antioxidants and modulators of redox signalling are able to provide an additional therapeutic effects, acting in synergy with ongoing treatments of the diseases and conditions having redox stress as a common denominator.