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.
Article info
Publication history
Published online: December 10, 2012
Accepted:
November 3,
2012
Received in revised form:
November 1,
2012
Received:
May 13,
2012
Identification
Copyright
© 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
