title: Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells.
abstract: Mn²⁺ is a minor nutrient, but is essential for numerous enzymatic activities and thus, for many cellular functions. However, its physiological roles and toxicity remain to be elucidated. In this study, we assessed the pharmacological potential and toxicity of Mn²⁺ in the immune system by examining the effects of Mn²⁺ on interleukin-2 (IL-2) production by Jurkat T-cells. Mn²⁺ at 0.1-1 mM did not significantly induce IL-2 production, whereas phorbol 12-myristate 13-acetate (PMA) at 1 μM slightly induced IL-2 production. Interestingly, Mn²⁺ at 0.3-0.7 mM promoted PMA-induced IL-2 production in a dose-dependent manner. A reporter gene assay revealed that Mn²⁺ promoted the activity of AP-1 (activator protein-1, a complex of c-Fos and c-Jun) in the presence of PMA. Western blot analysis showed that Mn²⁺ promoted the activation of JNK2 (c-Jun N-terminal kinase 2) and p38 MAPK (mitogen-activated protein kinase), which are both activators of AP-1, and upregulated the production of c-Fos and c-Jun within 4h in the presence of PMA. These results suggest that Mn²⁺ promotes PMA-induced IL-2 production by inducing the production and activation of AP-1, at least in part.
authors.affiliation: Department of Health and Nutrition, Faculty of Health and Welfare, Takasaki University of Health and Welfare, Takasaki 370-0033, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Masuda
authors.forename: Chihiro
authors.initials: C
authors.lastname: Honma
authors.forename: Kohei
authors.initials: K
authors.lastname: Hosaka
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kubohara
mesh_terms: D015153:Blotting, Western; D019703:Calcineurin / Q000096:biosynthesis / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology* / Q000633:toxicity*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D017895:Manganese Compounds / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology* / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D002712:Chlorides; D007376:Interleukin-2; D017895:Manganese Compounds; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; D013755:Tetradecanoylphorbol Acetate; C025340:manganese chloride