title: Role of NF-κB in epithelial biology.
abstract: Since its discovery, nuclear factor-κB (NF-κB) has been recognized as a critical regulator of immune responses. While early studies focused on studying the role of NF-κB in the development and function of immune cells, more recently the function of the inhibitor of NF-κB kinase (IKK)/NF-κB pathway in non-immune cells has gained increased attention. Studies in genetic mouse models were instrumental in dissecting the cell-specific functions of NF-κB and provided experimental evidence that NF-κB signaling in epithelial cells is important for the maintenance of immune homeostasis in barrier tissues such as the skin and the intestine. Increased activation of IKK/NF-κB triggered cytokine expression by the epithelial cells, resulting in exacerbated tissue inflammatory responses. NF-κB inhibition in keratinocytes triggered severe tumor necrosis factor-dependent skin inflammation and epidermal hyperplasia, while inhibition of IKK/NF-κB signaling in intestinal epithelial cells disturbed the intestinal barrier and triggered severe chronic colon inflammation. Therefore, epithelial NF-κB signaling performs critical 'peace keeping' functions in barrier tissues at the interface with the environment by regulating cell survival, barrier integrity, and the immunological and anti-microbial responses of epithelial cells. Improved understanding of epithelial NF-κB functions may hold the key for elucidating the etiology and pathophysiology of chronic inflammatory diseases in epithelial tissues.
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany. pasparakis@uni-koeln.de
authors.forename: Manolis
authors.initials: M
authors.lastname: Pasparakis
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism
chemical_list: D016328:NF-kappa B