NF-κB: an essential transcription factor in psoriasis

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.