Browsing by Author "Bruvere, Ruta"

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    Ageing and production of the cytokines in Chernobyl clean-up workers from Latvia
    (2009) Kurjane, Nataļja; Bruvere, Ruta; Gabruševa, Natalija; Hagina, Elvira; Zvagule, Tija; Jaunalksne, Inta; Feldmane, Guna; Volrate, Arija; Voskresenska, Natalija
    Chronic low-grade inflammation with subsequent impairment of immune system function promotes the development of age-related diseases, such as cancers, degenerative and infection diseases. It is not yet clear, if exposure to ionising radiation accelerates the aging process. The aim of the present work was to estimate the production of several cytokines by peripheral blood cells of Latvia's Chernobyl clean-up workers depending on age. ELISA was employed to determine the plasma level of sIL-1β and sIL-6 as well as level of IL-4 and TNF-α spontaneous and 24h and 96h after in vitro stimulation of peripheral blood mononuclear cell cultures by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) mitogens were determined in 40 Chernobyl clean-up workers 17 years after their work in Chernobyl and in 42 blood-donors without a history of occupational radiation exposure. The ability of peripheral blood leukocytes (PBL) to produce interferons (IFNs) was determined in 73 Chernobyl clean-up workers 15 years after the work in Chernobyl and in age-matched 63 blood-donors. IFNs were tested in whole blood cultures by standard virus cytopathic inhibition micromethod after their in vitro induction by Newcastle disease virus, phytohemagglutinin or double-stranded RNA. Individuals were divided into three age groups: age < 40, age 40-49 and age > 50. The ability of PBL to produce IFN was significantly decreased in all Chernobyl clean-up worker age groups in comparison with blood-donors (control groups). The incidence of good ability to produce IFN gradually decreased with age in the control group, but increased with age in aged-matched Chernobyl clean-up workers groups. The production TNF-α and IL-4 by peripheral blood mononuclear cells as well as sIL-1β level in plasma showed no significant differences between all the examined age groups. The sIL-6 level was gradually increased with age in Chernobyl clean-up workers. Our results showed that the concentration of pro-inflammation cytokine sIL-6 in peripheral blood plasma, as well as the ability of PBL to produce IFNs, in Chernobyl clean-up workers from Latvia is age dependent.
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    The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response
    (2019-02-28) Jansons, Juris; Sominskaya, Irina; Petrakova, Natalia; Starodubova, Elizaveta S.; Smirnova, Olga A.; Alekseeva, Ekaterina; Bruvere, Ruta; Eliseeva, Olesja; Skrastina, Dace; Kashuba, Elena; Mihailova, Marija; Kochetkov, Sergey N.; Ivanov, Alexander V.; Isaguliants, Maria G.; Department of Pathology
    HCV core is an attractive HCV vaccine target, however, clinical or preclinical trials of core-based vaccines showed little success. We aimed to delineate what restricts its immunogenicity and improve immunogenic performance in mice. We designed plasmids encoding full-length HCV 1b core and its variants truncated after amino acids (aa) 60, 98, 152, 173, or up to aa 36 using virus-derived or synthetic polynucleotides (core191/60/98/152/173/36_191v or core152s DNA, respectively). We assessed their level of expression, route of degradation, ability to trigger the production of reactive oxygen species/ROS, and to activate the components of the Nrf2/ARE antioxidant defense pathway heme oxygenase 1/HO-1 and NAD(P)H: quinone oxidoreductase/Nqo-1. All core variants with the intact N-terminus induced production of ROS, and up-regulated expression of HO-1 and Nqo-1. The capacity of core variants to induce ROS and up-regulate HO-1 and Nqo-1 expression predetermined their immunogenicity in DNA-immunized BALB/c and C57BL/6 mice. The most immunogenic was core 152s, expressed at a modest level and inducing moderate oxidative stress and oxidative stress response. Thus, immunogenicity of HCV core is shaped by its ability to induce ROS and oxidative stress response. These considerations are important in understanding the mechanisms of viral suppression of cellular immune response and in HCV vaccine design.