Nuclear factor-kappa B in intestinal protection and destruction.
OBJECTIVE
Nuclear factor-kappa B (NF-kappaB) is a key transcriptional regulator of innate and adaptive immunity. This review highlights new insights into the functions of NF-kappaB in normal homeostasis and specific disease processes in the intestinal tract.


RESULTS
Inflammatory bowel disease and experimental intestinal inflammation are characterized by NF-kappaB activation and increased expression of proinflammatory NF-kappaB target genes. Accordingly, NF-kappaB inhibition protects against chronic intestinal inflammation and necrotizing enterocolitis in animal models. However, recent findings suggest that NF-kappaB has not only proinflammatory but also tissue-protective functions. Thus, genetic ablation of the regulatory subunit, IkappaB kinase (IKK)gamma, of the central kinase complex required for NF-kappaB activation, IKK, or of both kinase subunits, IKKalpha and IKKbeta, in intestinal epithelial cells causes spontaneous murine colitis. Pharmacological inhibition of IKKbeta, and loss of IKKbeta or NF-kappaB p65 in the epithelium, sensitizes mice to acute inflammatory and injurious challenges. Deficiency in Toll-like receptor 5, a strong activator of NF-kappaB, results in spontaneous colitis and exacerbates mucosal inflammatory responses to Salmonella infection. Conversely, Toll-like receptor 5 stimulation confers radioprotection in the intestine.


CONCLUSIONS
NF-kappaB has multiple, often opposing functions in the intestine. Antiapoptotic actions of NF-kappaB in intestinal epithelial cells dominate tissue responses to many acute inflammatory and injurious challenges, whereas proinflammatory and cell survival functions of NF-kappaB in macrophages and T cells govern chronic intestinal inflammation.
Spehlmann
Martina E
ME
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0063, USA.
Eckmann
Lars
L
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D002056:Burns / Q000276:immunology; D018450:Disease Progression; D020345:Enterocolitis, Necrotizing / Q000276:immunology; D006706:Homeostasis / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000293:injuries; D007511:Ischemia / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D011832:Radiation Injuries / Q000276:immunology
D016328:NF-kappa B