Rheumatoid arthritis (RA) is a complex process of chronic and progressive
inflammation associated with activation of numerous signaling molecules and
transcription factors and hyperproliferation of synoviocytes of the affected joints, although the greater part of its pathophysiological process is explained by activation of
nuclear factor kappaB (
NF-kappaB). For example, the self-perpetuating nature of the rheumatoid
inflammation is ascribable to overexpression of the proinflammatory
cytokines tumor necrosis factor alpha and
interleukin-1beta, known to elicit the activation cascade for
NF-kappaB and
activator protein-1 that are responsible for transcriptional induction of these
cytokines among other target genes, which conform a positive feedback loop for continuation and expansion of the inflammatory responses. In addition, comparative gene expression profile analyses have revealed activation of a number of genes that explain the "transformed-like" phenotype of synoviocytes. Among the genes expressed in rheumatoid synoviocytes upon inflammatory stimuli, induction of gene expression of
Notch proteins and its
ligand have been found. Possible roles of Notch signaling in RA synoviocytes are discussed.