title: Interferon stimulated gene 15 has an anti-apoptotic effect on MIN6 cells.
abstract: Type 1 diabetes, one of two major forms of diabetes, results from the complete destruction of pancreatic beta cells. Viral infection has been suggested to be a trigger of beta cell destruction, the pathogenesis of type 1 diabetes. The aim of this study was to clarify the role of the protein encoded by intherferon stimulated gene (ISG) 15, an antiviral effector, in the development of this clinical entity. We used the mouse beta cell line MIN6 to investigate the role of ISG15 and paid special attention to apoptosis. Although not detected in native MIN6 cells, free ISG15 and ISG15 conjugated proteins were both present in dose-dependently increased amounts following stimulation with interferon alpha. As assessed both by caspase 3/7 activity and an annexin V assay, the percentage of apoptotic MIN6 cells (after exposure to the inflammatory cytokines of interleukin-1beta plus interferon gamma or tumor necrosis factor alpha) was decreased by pretreatment with adenovirus-expressing ISG15 and increased by expressing a short hairpin RNA directed against ISG15. In conclusion, ISG15 has an anti-apoptotic effect on MIN6 cells. Thus, promoting ISG15 expression in the pancreatic beta cells could be a potential therapeutic approach for patients with type 1 diabetes.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakata
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukui
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miyata
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D014452:Ubiquitins / Q000096:biosynthesis / Q000502:physiology
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D016898:Interferon-alpha; D053583:Interleukin-1beta; D014452:Ubiquitins; D007371:Interferon-gamma