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Rheumatoid arthritis is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis leading to joint destruction and ultimately dis-ability. In the inflamed RA joint the synovium is highly infiltrated by CD4 + T cells, B cells and macrophages, and the intimal lining becomes hyperplastic owing to the increased number of macrophage-like and fibro-blast-like synoviocytes. | ỊFEBS Journal MINIREVIEW Molecular aspects of rheumatoid arthritis role of transcription factors Hiroshi Okamoto1 Thomas P. Cujec2 Hisashi Yamanaka1 and Naoyuki Kamatani1 1 Institute of Rheumatology Tokyo Women s MedicalUniversity Japan 2 Ambrx Inc. La Jolla CA USA Keywords NFAT NF-kB rheumatoid arthritis transcription factors Correspondence H. Okamoto Institute of Rheumatology Tokyo Women s MedicalUniversity 10-22 Kawada-cho Shinjuku Tokyo 162-0054 Japan Fax 81 3 5269 1726 Tel 81 3 5269 1725 E-mail hokamoto@ior.twmu.ac.jp Received 14 March 2008 accepted 22 May 2008 doi 10.1111 j.1742-4658.2008.06582.x Rheumatoid arthritis is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis leading to joint destruction and ultimately disability. In the inflamed RA joint the synovium is highly infiltrated by CD4 T cells B cells and macrophages and the intimal lining becomes hyperplastic owing to the increased number of macrophage-like and fibroblast-like synoviocytes. This hyperplastic intimal synovial lining forms an aggressive front called pannus which invades cartilage and bone structures leading to the destruction and compromised function of affected joints. This process is mediated by a number of cytokines tumor necrosis factor-a interleukin-1 interleukin-6 interleukin-17 interferon-y etc. chemokines monocyte chemoattractant protein-1 monocyte chemoattractant protein-4 CCL18 etc. cell adhesion molecules intercellular adhesion molecule-1 vascular cell adhesion molecule-1 etc. and matrix metalloproteinases. Expression of these molecules is controlled at the transcription level and activation of a limited number of transcription factors is involved in this process. The central dogma of molecular biology is that DNA produces RNA which in turn produces protein. In the process of transcription RNA is produced from the DNA and this conversion is an essential element in gene expression.
