title: The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: involvement of interleukin-2 system.
abstract: Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell-cell interaction in multi-cellular eukaryotes. This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 amino acids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases the mRNA levels of the β and γ subunits of IL-2 receptor (IL-2R), while the mRNA levels of the α subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2Rα subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U-373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U-373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth.
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), University of Tuscia, Viterbo, Italy. d.cervia@unitus.it
authors.forename: Davide
authors.initials: D
authors.lastname: Cervia
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Catalani
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Belardinelli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Perrotta
authors.forename: Simona
authors.initials: S
authors.lastname: Picchietti
authors.forename: Claudio
authors.initials: C
authors.lastname: Alimenti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fausto
authors.forename: Adriana
authors.initials: A
authors.lastname: Vallesi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016798:Ciliophora / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016812:Euplotes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000276:immunology / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010675:Pheromones / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D008565:Membrane Proteins; D010675:Pheromones; D015800:Protozoan Proteins; D015375:Receptors, Interleukin-2; D051820:TCF Transcription Factors; C057783:mating pheromone Er-1, Euplotes raikovi