Jan. 4, 2010 Researchers led by Dr. Terrence A. Barrett of Northwestern University Medical School in Chicago. Illinois have discovered that activation of NF-κB, an inflammatory mediator, results in diarrhea in inflammatory bowel disease (IBD).
These results are presented in the January 2010 issue of the American Journal of Pathology.
IBD, which affects approximately 1 in 500 people in the United States, describes a group of diseases, including Crohn's disease and ulcerative colitis, with inflammation in the intestinal tract. Patients with IBD experience diverse symptoms, including abdominal pain, vomiting, diarrhea, bloody stools, and weight loss.
Immune responses contribute to mucosal permeability, and hence diarrhea, in IBD; however, the mechanisms that govern this response are not completely understood. Tang et al therefore examined the role of NF-κB, an inflammatory mediator, in IBD-induced diarrhea. Following immune activation, blocking NF-κB expression in the cells lining the intestinal tract inhibited diarrhea and prevented protein changes in these cells, resulting in decreased leakiness between the cells. These findings suggest that immune cell-mediated activation of NF-κB in IBD promotes the movement of fluid into the bowel lumen, resulting in diarrhea.
Tang et al. suggest that "NF-κB activation opens paracellular spaces and promotes movement of fluid into bowel lumen. … Importantly, changes in permeability were associated with a net movement of water and solute into the bowel lumen. These data not only correlated with clinical signs of diarrhea but also help explain the initial fluid accumulation observed in previous studies."
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- Tang Y, Clayburgh DR, Mittal N, Goretsky T, Dirisina R, Zhang Z, Kron M, Ivancic D, Katzman RB, Grimm G, Lee G, Fryer J, Nusrat A, Turner JR, Barrett TA. Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation. American Journal Of Pathology, 2010; 176 (1): 158 DOI: 10.2353/ajpath.2010.090548
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