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Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents


ISSN (Print): 1568-0142
ISSN (Online): 1875-6131

NF-κB as a Therapeutic Target for Transcription Factor Decoy Strategy in Inflammatory Diseases

Author(s): Naruya Tomita, Ryuichi Morishita, Tetsuya Tomita, Haruhito Azuma and Toshio Ogihara

Volume 2, Issue 1, 2003

Page: [51 - 56] Pages: 6

DOI: 10.2174/1568014033355826

Price: $65


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.

Keywords: transcription factor, decoy, gene therapy, glomerulonephritis, rheumatoid arthritis, myocardial infarction, transplantation

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