title: IL-2-induced IL-5 synthesis, but not proliferation, of human CD4+ T cells is suppressed by FK506.
abstract: Regulation of T cell IL-5 synthesis was investigated using human Th cell clones. Immunosuppressant FK506 suppressed IL-5 synthesis of T cells activated through TCR in a dose-dependent manner. IL-5 gene transcription and protein synthesis were also induced in the same T cell clones upon stimulation with IL-2 and were suppressed by FK506 in a dose response similar to that induced by TCR stimulation. In contrast to TCR stimulation, neither activating protein-1, nuclear factor-AT (NF-AT), nor NF-kappaB binding activity was significantly up-regulated by IL-2 stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was transcribed upon either TCR or IL-2 stimulation and was clearly down-regulated by FK506, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contained FK506-sensitive enhancer elements. Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Suko
authors.forename: O
authors.initials: O
authors.lastname: Kaminuma
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: A
authors.initials: A
authors.lastname: Hoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Asakura
authors.forename: E
authors.initials: E
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Miyazawa
authors.forename: C
authors.initials: C
authors.lastname: Nosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Okumura
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Okudaira
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis*; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D016559:Tacrolimus