V. V. Novitskii

Role of NF-kB, p53, and p21 in the Regulation of TNF-α Mediated Apoptosis of Lymphocytes

The effect of recombinant TNF-α on programmed death of donor lymphocytes was studied in vitro. The proapoptotic effect of this cytokine is realized through transcription factors and cell cycle inhibitors. Incubation of lymphocytes with recombinant TNF-α revealed increased levels of NF-kB and p21 and reducted content of nonphosphorylated p53.

Role of genetically determined production of immunoregulatory cytokines in immunopathogenesis of chronic viral hepatitides.

Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions −330G and −592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.

Chronic tick-borne encephalitis virus antigenemia: possible pathogenesis pathways.

Study of the proliferative potential and immunophenotype of lymphocytes and cytokine-producing capacity of mononuclear cells in patients with chronic tick-borne encephalitis virus antigenemia showed changes in T cell lymphoproliferative response, relative content of T cells and T helper inductors, immunoregulatory index, and imbalance in the production of immunoregulatory Th1 and Th2 cytokines.

Functional activity of Th-17 lymphocytes in pulmonary tuberculosis.

Increased content of CD4+CD161+IL-17A+ Th17 lymphocytes in the peripheral blood was found in patients with pulmonary tuberculosis irrespective of the clinical form (infiltrative, disseminated) and variant of the disease (drug-sensitive, drug-resistant). The elevated content of Th17 cells in pulmonary tuberculosis is associated with hypersecretion of Th17-associated cytokines IL-17A and IL-22 in vitro that was most pronounced (in case of IL-17A) in patients with disseminated pulmonary tuberculosis.

Effects of HSP27 Chaperone on THP-1 Tumor Cell Apoptosis

The role of Hsp27 (heat shock protein 27) chaperone in regulation of THP-1 tumor cell apoptosis was studied. Realization of tumor cell apoptosis under conditions of in vitro culturing with Hsp27 specifi c inhibitor (KRIBB3) was evaluated by fluorescent microscopy with FITC-labeled annexin V and propidium iodide. Measurements of Bcl-2 family proteins (Bcl-2, Bax, Bad) in tumor cells incubated with Hsp27 inhibitor were carried out by Western blotting. Chaperone Hsp27 acted as apoptosis inhibitor in THP-1 tumor cells modulating the proportion of antiapoptotic (Bcl-2) and proapoptotic (Bax and Bad) proteins.

Changes in the lipid phase of erythrocyte membranes in patients with paranoid schizophrenia.

Considerable changes in the lipid phase of erythrocyte membranes were found in patients with paranoid schizophrenia. During exacerbation and remission of the disease the content of phosphatidylethanolamine decreases, while the amount of lysophosphatidylcholine decreases. These changes are accompanied by an increase in erythrocyte membrane microviscosity. Structural modification of the lipid phase in erythrocyte membranes in patients with schizophrenia is associated with intensification of lipid peroxidation.

Typical Changes of Erythrocytes in Chronic Inflammation

Structural and metabolic status and function of erythrocytes were studied in patients with chronic bronchitis, chronic inflammatory diseases of the upper airways, and chronic colitis. Complex study of the peripheral component of the erythron showed that disorders in erythrocyte morphology and function (decreased erythrocyte dry weight, low concentration of sulfhydryl groups and lipoproteins, decreased content of high molecular weight polypeptides in parallel with increased content of low molecular weight proteins, increased number of transformed cells, and enhanced reversible aggregation) were nonspecific and did not depend on the location of the inflammatory process.

Cytogenetic disorders in peripheral blood lymphocytes of patients with febrile form of tick-borne encephalitis.

An appreciable increase in the number of aberrant lymphocytes was detected in the peripheral blood of patients with febrile form of tick-borne encephalitis (TBE). This increase peaked during week 2 of the infectious process and was paralleled by a decrease in the count of natural killer cells. By the end of the acute period of neuroinfection the number of cells with structural chromosome aberrations decreased, but still surpassed the control (donor blood). Genetically unstable cells were eliminated predominantly at the expense of lymphocytes with chromatid disorders, while the count of CD16-expressing lymphocytes increased. The intensity of reparative DNA synthesis was suppressed during the entire acute period of tick-borne encephalitis.

Role of Glutathione System Redox Potential in Apoptosis Dysregulation in MCF-7 Breast Adenocarcinoma

MCF-7 breast cancer cells and HBL-100 breast epithelial cells were cultured with N-ethylmaleimide, a blocker of SH groups. Changes in redox potential of the glutathione system, activities of glutathione reductase, glutathione peroxidase, and intensity of apoptotic cell death were evaluated. The results indicate that incubation with N-ethylmaleimide led to glutathione system imbalance, reduced tumor cell redox potential, and induced their programmed death, which seemed useful for prospective target therapy of tumor diseases.

Structure and Properties of Lipid Bilayer of Erythrocyte Membranes in Patients with Malignant Tumors

The study of erythrocyte membranes in untreated patients with malignant tumors of different location (lung cancer, tumors of the head and neck, stomach and colorectal cancer) revealed changes in the fatty-acid spectrum of phospholipid fraction paralleled by an increase in the viscosity of the lipid bilayer, including the area of protein-lipid contacts. The degree of changes depended on tumor location.