Kojima Hirotada, Inoue Toshiaki, Kunimoto Hiroyuki, Nakajima Koichi
Department of Immunology; Osaka City University Graduate School of Medicine; Osaka, Japan.
Division of Human Genome Science; Department of Molecular and Cellular Biology; School of Life Sciences; Faculty of Medicine; Tottori University; Yonago, Japan.
JAKSTAT. 2013 Oct 1;2(4):e25763. doi: 10.4161/jkst.25763. Epub 2013 Jul 22.
Cytokines play several roles in developing and/or reinforcing premature cellular senescence of young cells. One such cytokine, interleukin-6 (IL-6), regulates senescence in some systems in addition to its known functions of immune regulation and promotion of tumorigenesis. In this review, we describe recent advances in studies on the roles of IL-6 and its downstream signal transducer and activator of transcription 3 (STAT3) in regulating premature cellular senescence. IL-6/sIL-6Rα stimulation forms a senescence-inducing circuit involving the STAT3-insulin-like growth factor-binding protein 5 (IGFBP5) as a key axis triggering and reinforcing component in human fibroblasts. We describe how cytokines regulate the process of senescence by activating STAT3 in one system and anti-senescence or tumorigenesis in other systems. The roles of other STAT members in premature senescence also will be discussed to show the multiple mechanisms leading to cytokine-induced senescence.
细胞因子在年轻细胞过早的细胞衰老发展和/或强化过程中发挥多种作用。其中一种细胞因子，白细胞介素-6（IL-6），除了其已知的免疫调节和促进肿瘤发生的功能外，还在某些系统中调节衰老。在本综述中，我们描述了关于IL-6及其下游信号转导和转录激活因子3（STAT3）在调节过早细胞衰老中作用的研究最新进展。IL-6/sIL-6Rα刺激形成了一个衰老诱导回路，该回路涉及STAT3-胰岛素样生长因子结合蛋白5（IGFBP5）作为人成纤维细胞中触发和强化衰老的关键轴。我们描述了细胞因子如何通过在一个系统中激活STAT3以及在其他系统中发挥抗衰老或促进肿瘤发生的作用来调节衰老过程。还将讨论其他STAT成员在过早衰老中的作用，以展示导致细胞因子诱导衰老的多种机制。
