title: NF-kappaB in inflammatory bowel disease.
abstract: Apart from genetic and environmental factors, the mucosal immune system of the gut plays a central role in the pathogenesis of inflammatory bowel disease (IBD). In the healthy gut, the mucosal immune system ensures the balance between pro- and anti-inflammatory mediators and thereby allows an effective defence against luminal pathogens but at the same time prevents an overwhelming immune reaction directed against the huge amount of harmless luminal antigens (for example, components of food or nonpathological bacteria). In both entities of IBD (Crohn's disease and ulcerative colitis) this immunological balance is severely impaired and shifted towards the pro-inflammatory side. The chronic mucosal inflammation in IBD is caused by hyperactivation of effector immune cells, which produce high levels of pro-inflammatory cytokines like tumour necrosis factor-alpha, interleukin-6 and interferon-gamma, resulting in colonic tissue damage. The nuclear transcription factor kappaB (NF-kappaB) was identified as one of the key regulators in this immunological setting. Its activation is markedly induced in IBD patients and through its ability to promote the expression of various pro-inflammatory genes, NF-kappaB strongly influences the course of mucosal inflammation. Considering the different cell-type specific effects which are mediated by NF-kappaB, this review aims at describing the complex role of NF-kappaB in IBD and discusses existing pharmacological attempts to block the activation of NF-kappaB to develop new therapeutic strategies in IBD.
authors.affiliation: Institute of Molecular Medicine and I. Medical Clinic, University of Mainz, Mainz, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Atreya
authors.forename: R
authors.initials: R
authors.lastname: Atreya
authors.forename: M F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D006801:Humans; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000628:therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D016328:NF-kappa B