Title: NF-κB as a Therapeutic Target for Transcription Factor Decoy Strategy in Inflammatory Diseases
Volume: 2
Issue: 1
Author(s): Naruya Tomita, Ryuichi Morishita, Tetsuya Tomita, Haruhito Azuma and Toshio Ogihara
Affiliation:
Keywords:
transcription factor, decoy, gene therapy, glomerulonephritis, rheumatoid arthritis, myocardial infarction, transplantation
Abstract: Nuclear factor (NF)-κB is a transcription factor associated with modulation of the immune response. NF-κB is a heterodimer consisting of subunits p50, p52 and p65 (Rel A) or Rel B or cRel (the most common NF-κB heterodimer consist of subunits p50 and p65) that belong to the Rel family of genes, which includes the v-rel oncogene, the c-rel protooncogene and dorsal, a Drosophia morphogen. In its quiesecent state, NF-κB is in the cytoplasm, bound to a family of inhibitory proteins that are collectively called IkB. Several molecules, including interleukin (IL)-1, lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, reactive oxygen intermediates and viral products activate NF-κB through phosphorylation and subsequent degradation of IkB. Activation by these agents leads to exposure of the nuclear localization signal of NF-κB and entry into the nucleus. Once in the nucleus, NF-κB transcriptionally activates a variety of genes involved in the inflammatory process, including intracellular adhesion molecule (ICAM)-1, vascular cellular adhesion molecule (VCAM)-1, endothelial leukocyte adhesion molecule (ELAM) and IL-8. The family of NF-κB transcription factor is a topic of interest in the biomedical community stemming from the role NF-κB plays in almost every aspect of cell regulation such as stress responses, immune cell activation, apoptosis, proliferation, differentiation and oncogenic transformation. Recently, we have developed a novel molecular strategy termed the decoy approach to inhibit NF-κB activity. Moreover, E2F decoy strategy has already been used in the clinical trials to prevent the vascular disease. Taken together, the decoy strategy is considered to have the potential of clinical application.
