title: Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells.
abstract: Cucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound. Here, its effects on CD4(+) T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system, were investigated. Production of major pathogenic Th cell cytokines: interferon-gamma and interleukin-17 were inhibited under the influence of CucE. The effects of CucE on CD4(+) T cells were mediated through the modulation of aryl hydrocarbon receptor, STAT3, NFκB, p38 MAPK, and miR-146 signaling. Further, production of nitric oxide and reactive oxygen species, as well as phagocytic ability, were inhibited in macrophages treated with CucE. These results imply that CucE possesses powerful antiencephalitogenic activity.
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade , Belgrade, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Jevtić
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade , Belgrade, Serbia.
authors.forename: Neda
authors.initials: N
authors.lastname: Djedović
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade , Belgrade, Serbia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Stanisavljević
authors.affiliation: Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade , Belgrade, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Despotović
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade , Belgrade, Serbia.
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljković
authors.affiliation: Laboratory for Plant Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade , Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Timotijević
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D014315:Triterpenes / Q000008:administration & dosage*; D015027:Zebrafish
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D014315:Triterpenes; D007371:Interferon-gamma; C102326:cucurbitacin E
keywords: T cell; autoimmunity; cucurbitacin E; experimental autoimmune encephalomyelitis; macrophage