title: Involvement of IL-32 in activation-induced cell death in T cells.
abstract: NK cell transcript 4 (NK4), now denoted as IL-32, was originally identified as a transcript whose expression was increased in activated NK cells. It has been very recently demonstrated that NK4 is secreted from several cells upon the stimulation of some inflammatory cytokines such as IL-18, IL-1beta, IFN-gamma and IL-12. Furthermore, NK4 induces production of tumor necrosis factor, macrophage inflammatory protein (MIP)-2 and IL-8 in monocytic cell lines, indicating that this factor would be involved in the inflammatory responses. Based on these findings, NK4 was renamed IL-32. However, the biological activities of IL-32 on other cell types remained undetermined. Furthermore, it was still argued whether IL-32 acts on cells from outside or inside the cells. In this article, we first report that expression of IL-32 was up-regulated in activated T cells and NK cells, and that IL-32beta was the predominantly expressed isoform in activated T cells. IL-32 was specifically expressed in T cells undergoing apoptosis and enforced expression of IL-32-induced apoptosis, whereas its down-regulation rescued the cells from apoptosis in HeLa cells. IL-32 existing in the supernatant would be derived from the cytoplasm of apoptotic cells. These results strongly indicated that IL-32 would be involved in activation-induced cell death in T cells, probably via its intracellular actions. Our present findings expand our understanding of the biological function of IL-32 and argue that IL-32 may act on cells, not only from the outside but also from the inside.
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Goda
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kanaji
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kanaji
authors.forename: Go
authors.initials: G
authors.lastname: Tanaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C496971:IL32 protein, human; D007378:Interleukins