| First Author | Jobin C | Year | 2000 |
| Journal | Am J Physiol Cell Physiol | Volume | 278 |
| Issue | 3 | Pages | C451-62 |
| PubMed ID | 10712233 | Mgi Jnum | J:60875 |
| Mgi Id | MGI:1354043 | Doi | 10.1152/ajpcell.2000.278.3.C451 |
| Citation | Jobin C, et al. (2000) The IkappaB/NF-kappaB system: a key determinant of mucosal inflammation and protection. Am J Physiol Cell Physiol 278(3):C451-62 |
| abstractText | The ubiquitous transcription factor NF-kappaB 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-kappaB profoundly influences mucosal inflammation and repair. NF-kappaB activation requires the removal of IkappaB from NF-kappaB by inducible proteolysis, which liberates this transcription factor for migration to the nucleus, where it binds to kappaB-regulatory elements and induces transcription. IkappaBalpha degradation is incomplete and delayed in IECs, resulting in buffered responses to luminal stimuli. The stimulatory environment partially determines whether the effect of NF-kappaB is protective or deleterious for the host. kappaB-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-kappaB in regulating expression of a number of proinflammatory genes makes this protein an attractive target for selective therapeutic intervention. |
