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The transcription factor, nuclear factor-κB (NF-κB), is a dominant regulator of the expression of hundreds of genes, many of which play important roles in the regulation of inflammation and programmed cell death (apoptosis). Since the discovery of NF-κB in the mid 1980s, this transcription factor has been the subject of intense investigation. Excess or inappropriate activation of NF-κB has been observed in human inflammatory bowel disease and in a host of other inflammatory diseases and type of cancer. Functional studies in animals have shed light on the role of NF-κB in broader pathophysiological contexts. From such studies, it has become quite clear that NF-κB plays unique and distinct functions in different cell types. Because of the importance of NF-κB in signaling inflammation, and in inhibiting programmed cell death, many pharmaceutical companies are developing small-molecule inhibitors of this pathway. In this article, we evaluate the relative pros and cons of blocking NF-κB as a therapeutic approach for inflammatory bowel disease. On the basis of the results of studies in animals that have primarily used genetic approaches to inhibit NF-κB activity, we suggest that there are certain niche indications for blocking NF-κB in inflammatory bowel disease that offer particular promise. [ABSTRACT FROM AUTHOR]

Transcription factor proteins regulate gene expression via binding to specific DNA sequences found in the promoter/enhancer regions of the genes they control. Although most transcription factor binding has been associated with an increase in gene expression, gene suppression has also been described. Transcription factor decoys are molecules that mimic the binding sites for transcription factor proteins, and compete with promoter regions to absorb this binding activity in the cell nucleus. By blocking transcription factor-chromosomal DNA interaction, these molecules provide a powerful means to manipulate the regulation of gene expression, particularly as transcription factors are increasingly understood to alter gene activation during the course of normal and pathologic processes in cell biology. As methods for cellular and nuclear delivery of these agents improve, the increasing use of transcription factor decoys, both as investigative and therapeutic tools, promises to have a significant impact on our understanding of and ability to treat human disease. [ABSTRACT FROM AUTHOR]