V. V. Novitsky

Allelic Polymorphism of Cytokine Genes during Pulmonary Tuberculosis

Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.

Psychoimmune Interactions in Women of Reproductive Age with Endometriosis

Psychoimmune interactions were studied in women of reproductive age with endometriosis. Pronounced immunological shifts manifested in a shift of the T-cellular immunity, resulting in imbalanced production of pro- (IL-1β, IL-2, IFN-γ) and anti-inflammatory (IL-4) cytokines. Significant correlations between the severity of mental shifts and immunopathogenetic factors in the studied patient population demonstrated the psychoneuroimmune nature of endometriosis.

Role of recombinant mitogen-activated protein kinases JNK and p38 in the regulation of apoptosis in blood mononuclear cells under conditions of oxidative stress in vitro

Programmed death of peripheral blood mononuclear cells from healthy donors was studied during culturing with various concentrations of H2O2 and selective inhibitors of JNK (SP600125) and p38 MAPK (ML3403). In vitro incubation of mononuclear leukocytes with 1 mM H2O2 stimulated apoptotic cell death. Treatment with inhibitors (SP600125 and ML3403) during in vitro oxidative stress prevented the increase in the number of annexin-positive mononuclear cells. Our results indicate that MAP kinases JNK and p38 are involved in the mechanisms of oxidative dysregulation of apoptosis.

Modulation of apoptosis of mononuclear cells under conditions of oxidative stress

We studied mitochondrial and type 1 tumor necrosis factor-α receptor (TNFR1)-mediated pathways triggering the apoptotic program in mononuclear cells under conditions of oxidative stress. Intensification of intracellular production of reactive oxygen forms is accompanied by an increase in the number of annexin-positive TNFR1-presenting cells and mononuclear cells with reduced mitochondrial transmembrane potential in case of induction of oxidative stress with 1 mM H2O2in vitro and in patients with pneumonia.

Regulatory Role of Nitric Oxide in Neutrophil Apoptosis

Apoptosis of blood neutrophils from healthy donors was studied under conditions of cell culturing with different concentrations of H2O2, selective NO synthase inhibitor, and inductor of NO synthesis (L-arginine). In vitro incubation of neutrophilic leukocytes with 5 mM H2O2 led to activation of the apoptotic program in neutrophils, which was seen from increased content of Bax protein in the cells and increased number of apoptotic cells in the culture. Increased content of annexin-positive cells after incubation of neutrophil culture with NO synthase inhibitor suggests involvement of NO in the regulation of neutrophil apoptosis under conditions of oxidative stress, while L-arginine prevented H2O2-induced programmed cell death.

The Role of the Glutathione System in Oxidative Modification of Proteins and Dysregulation of Apoptosis in Jurkat Tumor Cells

We compared changes in the redox status and intensity of oxidative modification of proteins in intact Jurkat tumor cells and cells cultured with buthionine sulfoximine, an inhibitor of the key enzyme of glutathione synthesis γ-glutamylcysteine synthetase. The glutathione system components play a role in modulation of the content of protein-bound glutathione, protein carbonyl derivatives, bityrosine, and oxidized tryptophan, and in dysregulation of apoptosis in Jurkat tumor cells. Inhibition of de novo synthesis of glutathione in Jurkat tumor cells was followed by accumulation of hydroxyl radical, a reduction in the level of protein-bound glutathione and oxidized tryptophan, and a rise in the concentration of protein carbonyl derivatives. These changes were accompanied by activation of programmed cell death.

Effect of insulin, the glutathione system, and superoxide anion radical in modulation of lipolysis in adipocytes of rats with experimental diabetes

Spontaneous lipolysis was found to be increased in adipocytes of rats with alloxan-induced diabetes. In addition, isoproterenol-stimulated hydrolysis of triacylglycerols was inhibited against the background of oxidative stress and decreased redox-status of cells. A decrease in the ability of insulin to inhibit isoproterenol-stimulated lipolysis in adipocytes that were isolated from adipose tissue of rats with experimental diabetes was found, which shows a disorder in regulation of lipolysis in adipocytes by the hormone in alloxan-induced diabetes. Based on these findings, we concluded that there is an influence of reactive oxygen species, superoxide anion radical in particular, and redox potential of the glutathione system on molecular mechanisms of change in lipolysis intensity in rat adipocytes in alloxan-induced oxidative stress. Activation of spontaneous lipolysis under conditions of oxidative stress might be a reason for the high concentration of free fatty acids in blood plasma in experimental diabetes, and this may play a significant role in development of insulin resistance and appearance of complications of diabetes

Cytokine-Secreting Activity of Blood Eosinophils in Pulmonary Tuberculosis

Modern immunological studies showed that eosinophilic granulocytes producing the key mediators of cellular and humoral immune response contribute to the common cytokine imbalance developing in tuberculous infection. A significant increase in BCG-induced secretion of IL-2, IL-5, and TNF-α by eosinophils in patients with pulmonary tuberculosis indicated high reserve reactivity of eosinophilic cells realizing their functional potential in regulation of the specific resistance reactions of the microorganism under conditions of M. tuberculosis infection.

Role of Thiol-Disulfide System in Mechanisms of Functional Changes in Neutrophils under Conditions of Oxidative Stress

We studied the state of the thiol-disulfide system (contents of reduced and oxidized glutathione, their ratio, and concentrations of protein SH-groups and protein-bound glutathione) and functional properties of neutrophils (production of hydroxyl radicals, IL-8, and TNF-α and myeloperoxidase activity) from healthy donors under conditions of oxidative stress in vitro induced by H2O2 in a final concentration of 200 μM and from patients with community-acquired pneumonia. We evaluated the role of reduced and protein-bound glutathione in the regulation of functional state of blood neutrophils from patients with community-acquired pneumonia and during oxidative stress in vitro under conditions cell incubation with N-ethylmaleimide or 1,4-dithioerythritolsulfhydryl, the blocker and protector of sulfhydryl groups, respectively.