NF-κB is an inducible transcription factor that is controlled by the signal activation cascades. NF-κB controls a number of genes involved in immuno-inflammatory responses, cell cycle progression, inhibition of apoptosis, and cell adhesion, thus promoting chronic inflammatory responses. In fact, NF-κB is constitutively activated in some rheumatic conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Interestingly, a number of anti-RA compounds have been shown to exhibit anti-NF-κB activities. In addition, NF-κB activation has been linked to carcinogenesis and its constitutive activation has been demonstrated in some cancers and leukemias. These findings have substantiated the long-standing proposal of the link among chronic inflammation, autoimmunity, and carcinogenesis by molecular terms. In this review, I have attempted to overview the pathologic involvement of NF-κB in rheumatic diseases and discuss the feasibility of a therapeutic strategy with NF-κB and its signaling cascade as novel molecular targets.
NF-κ B, signal transduction, IKK, transcription, apoptosis, inflammation, autoimmunity, rheumatoid arthritis, systemic lupus erythematosus, inhibitors
Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.