NF-kappaB and rheumatic diseases.
NF-kappaB is an inducible transcription factor that is controlled by the signal activation cascades. NF-kappaB 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-kappaB 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-kappaB activities. In addition, NF-kappaB 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-kappaB in rheumatic diseases and discuss the feasibility of a therapeutic strategy with NF-kappaB and its signaling cascade as novel molecular targets.
Okamoto
Takashi
T
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. tokamoto@med.nagoya-cu.ac.jp
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D053264:B-Cell Activating Factor / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000503:physiopathology; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology; D010766:Phosphorylation; D012216:Rheumatic Diseases / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; D016328:NF-kappa B; C505719:TNFSF13B protein, human