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Ann N Y Acad Sci. 2006 Aug;1072:114-22.

NF-kappaB signaling: pros and cons of altering NF-kappaB as a therapeutic approach.

Author information

1
Clinical Science Institute, University College Hospital, Galway, Ireland. laurence.egan@nuigalway.ie

Abstract

The transcription factor, nuclear factor-kappaB (NF-kappaB), 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-kappaB in the mid 1980s, this transcription factor has been the subject of intense investigation. Excess or inappropriate activation of NF-kappaB 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-kappaB in broader pathophysiological contexts. From such studies, it has become quite clear that NF-kappaB plays unique and distinct functions in different cell types. Because of the importance of NF-kappaB 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-kappaB 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-kappaB activity, we suggest that there are certain niche indications for blocking NF-kappaB in inflammatory bowel disease that offer particular promise.

PMID:
17057194
DOI:
10.1196/annals.1326.009
[Indexed for MEDLINE]

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