The IκB/NF-κB system:: a key determinant of mucosal inflammation and protection

被引:341
作者
Jobin, C
Sartor, RB
机构
[1] Univ N Carolina, Dept Med, Div Digest Dis & Nutr, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2000年 / 278卷 / 03期
关键词
cytokines; signal transduction; bacteria; gene manipulation; intestinal epithelial cells;
D O I
10.1152/ajpcell.2000.278.3.C451
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The ubiquitous transcription factor NF-kappa 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-kappa B profoundly influences mucosal inflammation and repair. NF-kappa B activation requires the removal of I kappa B from NF-kappa B by inducible proteolysis, which liberates this transcription factor for migration to the nucleus, where it binds to kappa B-regulatory elements and induces transcription. I kappa B alpha degradation is incomplete and delayed in IECs, resulting in buffered responses to luminal stimuli. The stimulatory environment partially determines whether the effect of NF-kappa B is protective or deleterious for the host. kappa 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-kappa B in regulating expression of a number of proinflammatory genes makes this protein an attractive target for selective therapeutic intervention.
引用
收藏
页码:C451 / C462
页数:12
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