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B/NF-B system: a key determinant of mucosal inflammation
and protection
Departments of 1 Medicine and 2 Microbiology and Immunology, and the 3 Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina 27599
The ubiquitous
transcription factor NF-
B is a central regulator of the
transcriptional activation of a number of genes involved in cell
adhesion, immune and proinflammatory responses, apoptosis, differentiation, and growth. Induction of these genes in intestinal epithelial cells (IECs) by activated NF-B profoundly influences mucosal inflammation and repair. NF-B activation requires the removal of IB from NF-B by inducible proteolysis, which liberates this transcription factor for migration to the nucleus, where it binds
to B-regulatory elements and induces transcription. IB
degradation is incomplete and delayed in IECs, resulting in buffered
responses to luminal stimuli. The stimulatory environment partially
determines whether the effect of NF-B is protective or deleterious
for the host. B-dependent proinflammatory gene expression,
particularly chemokines, major histocompatibility complex
class II antigens, and adhesion molecules may be extremely important in
early protective responses to mucosal pathogens but, when dysregulated,
could lead to the development of chronic inflammation, as seen in
inflammatory bowel diseases. The key role of NF-B in regulating
expression of a number of proinflammatory genes makes this protein an
attractive target for selective therapeutic intervention.
cytokines; signal transduction; bacteria; gene manipulation; intestinal epithelial cells
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