Nuclear factor-kappa B in Intestinal protection and destruction

Purpose of review Nuclear factor-kappa B (NF-kappa B) is a key transcriptional regulator of innate and adaptive immunity. This review highlights new insights into the functions of NF-kappa B in normal homeostasis and specific disease processes in the intestinal tract. Recent findings Inflammatory bowel disease and experimental intestinal inflammation are characterized by NF-kappa B activation and increased expression of proinflammatory NF-kappa B target genes. Accordingly, NF kappa B inhibition protects against chronic intestinal inflammation and necrotizing enterocolitis in animal models. However, recent findings suggest that NF-kappa B has not only proinflammatory but also tissue-protective functions. Thus, genetic ablation of the regulatory subunit, I kappa B kinase (IKK)gamma, of the central kinase complex required for NF-kappa B activation, IKK, or of both kinase subunits, IKK alpha and IKK beta, in intestinal epithelial cells causes spontaneous murine colitis. Pharmacological inhibition of IKK beta, and loss of IKK beta or NF-kappa B p65 in the epithelium, sensitizes mice to acute inflammatory and injurious challenges. Deficiency in Toll-like receptor 5, a strong activator of NF-kappa B, results in spontaneous colitis and exacerbates mucosal inflammatory responses to Salmonella infection. Conversely, Toll-like receptor 5 stimulation confers radioprotection in the intestine. Summary NF-kappa B has multiple, often opposing functions in the intestine. Antiapoptotic actions of NF-kappa B in intestinal epithelial cells dominate tissue responses to many acute inflammatory and injurious challenges, whereas proinflammatory and cell survival functions of NF-kappa B in macrophages and T cells govern chronic intestinal inflammation.