title: Modulation of murine EL-4 thymic lymphoma cell proliferation and cytokine production by vitamin E succinate.
abstract: RRR-alpha-tocopheryl succinate (VES) was studied for effects on murine EL-4 cell proliferation and production of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-beta). VES was biphasic in its actions: 0.1 microgram/ml enhanced EL-4 cell proliferation, whereas 10-20 microgram/ml inhibited cellular proliferation. Cell-conditioned media (CM) from EL-4 cells treated with 0.2 ng/ml phorbol myristate acetate (PMA) + 0.1 microgram/ml VES contained increased amounts of IL-2, as determined by the murine cytotoxic T cell IL-2-dependent CTLL-2 bioassay. VES at 0.1 microgram/ml or 0.1 microgram/ml VES + 0.2 ng/ml PMA induced the expression of IL-2 mRNA by EL-4 cells three to nine hours after treatment. CM from EL-4 cells treated with VES at 10-20 microgram/ml exhibited potent antiproliferative activity when tested in the TGF-beta-responsive mink lung cell (Mv1Lu) bioassay and showed reduced inhibitory effects when tested on TGF-beta receptor-negative mink lung (DRA-27) cells. CM from control-treated EL-4 cells exhibited no antiproliferative activity. The VES-induced antiproliferative activity was characterized as TGF-beta by neutralization analyses and immunoprecipitation of metabolically labeled proteins with TGF-beta-specific reagents. VES treatment of EL-4 cells had no effect on TGF-beta 1 mRNA expression while downregulating TGF-beta 3 mRNA expression. In summary, these studies showed that 0.1 microgram/ml VES enhanced cellular proliferation, in part, via increased IL-2 production, whereas 10-20 micrograms/ml VES inhibited cellular proliferation, in part, via the secretion of biologically active TGF-beta.
authors.affiliation: Genetics Institute, University of Texas, Austin 78712, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: B G
authors.initials: BG
authors.lastname: Sanders
authors.forename: K
authors.initials: K
authors.lastname: Kline
mesh_terms: D000818:Animals; D002455:Cell Division; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013945:Thymoma / Q000378:metabolism* / Q000473:pathology*; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology*; D024505:Tocopherols; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D013755:Tetradecanoylphorbol Acetate; D024505:Tocopherols