title: Inhibition of cytokine gene transcription by the human recombinant histamine-releasing factor in human T lymphocytes.
abstract: Human recombinant histamine-releasing factor (HrHRF) preincubation enhances the secretion of histamine, IL-4, and IL-13 from FcepsilonRI-stimulated human basophils. In GM-CSF-primed human eosinophils, HrHRF increases IL-8 production. Our recent experiments were designed to evaluate the effects of HrHRF on human T cell cytokine production. Purified T cells were preincubated with GST-tagged HrHRF, followed by stimulation with PMA and A23187 overnight. A partial inhibition of IL-2 and IL-13 production (30 and 75%, respectively) was detected compared with that in cells treated with PMA/A23187 alone. However, the production of IFN-gamma was similar in PMA/A23187 stimulated cells with or without HrHRF. The inhibition of cytokine protein production was dose dependent and specific to the HrHRF portion of GST-HrHRF. The inhibition was not due to endotoxin, since preincubation with polymyxin B and HrHRF gave similar results to that with HrHRF alone. The same pattern and specificity of cytokine regulation were replicated in the Jurkat T cell line as for primary T cells. The PMA/A23187-stimulated activity of a proximal promoter IL-13, IL-4, or IL-2 luciferase construct transfected into Jurkat cells was partially inhibited (60, 32, or 70%, respectively) upon GST-HrHRF preincubation, suggesting that HrHRF functions to inhibit cytokine production in Jurkat cells by preventing gene transcription. The inhibition of IL-2 promoter activation was specific to the HrHRF portion of GST-HrHRF. We conclude that HrHRF, in addition to functioning as a histamine-releasing factor, can differentially modulate the secretion of cytokines from human basophils, eosinophils, T cells, and murine B cells, suggesting that it may induce a complex array of responses at sites of allergic inflammation.
mesh_terms: D017209:Apoptosis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000494:pharmacology / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000276:immunology; D006636:Histamine Release / Q000235:genetics / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000276:immunology*; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D018106:CD28 Antigens; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D000090324:Tumor Protein, Translationally-Controlled 1; D015847:Interleukin-4; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate