title: IL-6-STAT3 signaling and premature senescence.
abstract: 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.
authors.affiliation: Department of Immunology; Osaka City University Graduate School of Medicine; Osaka, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Division of Human Genome Science; Department of Molecular and Cellular Biology; School of Life Sciences; Faculty of Medicine; Tottori University; Yonago, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Immunology; Osaka City University Graduate School of Medicine; Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kunimoto
authors.affiliation: Department of Immunology; Osaka City University Graduate School of Medicine; Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajima
keywords: IGFBP5; STAT3; cellular senescence; cytokine; interleukin-6; tumorigenesis