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NF-κB: An essential transcription factor in psoriasis

Published:December 10, 2012DOI:https://doi.org/10.1016/j.jdermsci.2012.11.002

      Abstract

      Nuclear factor kappa B (NF-κB) is a protein transcription factor that orchestrates inflammation and other complex biological processes. It is a key regulatory element in a variety of immune and inflammatory pathways, in cellular proliferation and differentiation and in apoptosis. Therefore NF-κB is a crucial mediator involved in the pathogenesis of psoriasis. Psoriasis, an inflammatory dermatosis, is marked by elevated levels of active, phosphorylated NF-κB. Genomic studies have also linked psoriasis with mediators in the NF-κB pathway. NF-κB has been hypothesized to connect the altered keratinocyte and immune cell behavior that characterizes the psoriatic milieu. Several anti-psoriatic therapies, including tumor necrosis factor-α blockers and glucocorticoids, reduce active NF-κB levels and related down-stream elements, and other biologics currently in development, including interleukin-17 blockers, may also target this pathway. Compounds that specifically target NF-κB signaling may be developed as novel therapeutics for chronic inflammatory disorders including psoriasis. However, chronic NF-κB inhibition could also result in immunodeficiencies. Therefore, a delicate balance must be found that maximizes therapeutic potential while limiting harmful effects, and may be achieved through several possible approaches, including localized therapy, selective inhibition of NF-κB signaling in pathologic cells, incomplete pathway inhibition or short treatment durations.

      Abbreviations:

      IκB (inhibitor of kappa B), IKK (inhibitor of kappa B kinase), IL (interleukin), NF-κB (nuclear factor kappa B), TNF (tumor necrosis factor), TRAF (TNF receptor associated factor)

      Keywords

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      Biography

      Dr. Lizzul is an investigator with the following: Abbott Laboratories, Amgen Inc., Celgene Corporation, Janssen Biotech Inc., National Institutes of Health, Novartis Pharmaceuticals Corp, Pfizer Inc. He is also on the advisory board for the National Institutes of Health. He is currently employed at and has stock ownership in Kythera biopharmaceuticals.

      Biography

      Dr Gottlieb currently receives honoraria from consulting/advisory board agreements with the following: Amgen Inc., Astellas, Janssen Biotech Inc., Celgene Corp., Bristol Myers Squibb Co., Beiersdorf Inc, Abbott Labs, TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd, Incyte, Pfizer, Canfite, Lilly, Coronado. She also has research/educational grants (paid to Tufts Medical Center) with the following: Janssen Biotech Inc., Amgen, Immune Control, Abbott, Novo Nordisk, UCB, Novartis, Celgene, Pfizer, Lilly. She is also employed by Tufts Medical Center.