Okamoto Takashi
Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Mod Rheumatol. 2005;15(2):79-86. doi: 10.1007/s10165-004-0372-8.
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.
类风湿性关节炎（RA）是一个复杂的慢性进行性炎症过程，与众多信号分子和转录因子的激活以及受累关节滑膜细胞的过度增殖有关，尽管其病理生理过程的大部分可通过核因子κB（NF-κB）的激活来解释。例如，类风湿性炎症的自我持续特性可归因于促炎细胞因子肿瘤坏死因子α和白细胞介素-1β的过度表达，已知这些细胞因子会引发NF-κB和激活蛋白-1的激活级联反应，它们负责这些细胞因子以及其他靶基因的转录诱导，这构成了炎症反应持续和扩展的正反馈回路。此外，比较基因表达谱分析揭示了许多基因的激活，这些基因解释了滑膜细胞的“转化样”表型。在炎症刺激下类风湿滑膜细胞中表达的基因中，已发现Notch蛋白及其配体的基因表达被诱导。本文讨论了Notch信号在RA滑膜细胞中的可能作用。
