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Biomedical subjects

S V Sennikov

Publications and source records attributed to S V Sennikov.

16 recordsLinked to original sources

Alternative splicing of murine interleukin-4 mRNA.

We found an alternative form of mRNA with spliced second exon (IL-4delta2 mRNA) in mouse bone marrow and splenic cells. At rest, the amount of IL-4 mRNA markedly surpassed that of IL-4delta2 mRNA. Stimulation increased the content of both mRNA forms, but the alternative variant is accumulated more intensively and rapidly. We did not detect predominance of IL-4delta2 mRNA over full-length mRNA variant in the studied mouse tissues.

Alternative Splicing↗

Alternative splicing of interleukin-6 mRNA in mice.

Expression of mRNA for interleukin-6, interleukin-6Delta3, and interleukin-6Delta5 was detected in placental tissue (second and third trimesters of pregnancy) and spleen of mice immunized with sheep erythrocytes in high dose. We hypothesize that translation of mRNA yields proteins capable of binding to individual subunits of the interleukin-6 receptor and possessing effector functions.

Alternative Splicing↗

[The use of electrochemoluminescent method for detection of cytokines in various media].

Electrochemiluminescent (ECL) method was used for cytokine detection with TAG label (ruthenium(II) tris-bipyridine chelate N-hydroxysuccinimide ester). A quantitative ECL detection of IL-4 and IFN-gamma in physiological fluids and cell culture media is described. The results evidence that ECL is compatible to commercial kits or even more effective. The advantages of ECL are simple procedure, no need in washings, small volume of the assay, wide range of cytokine concentrations, high sensitivity, and good reproducibility. The method can be used in research and clinical laboratories.

Animals↗

Regulation of functional activity of bone marrow hemopoietic stem cells by erythroid cells in mice.

Transplantation of erythroid and bone marrow cells to irradiated mice stimulated exogenous colony formation. Pretreatment of erythroid cells with specific rabbit antiserum to erythroblasts abolished this effect. The reverse transcriptase polymerase chain reaction revealed the presence of mRNA for interleukin-1alpha, interleukin-1beta, interleukin-3, interleukin-6, and granulocyte-macrophage colony-stimulating factor in erythroid cells. Granulocyte-macrophage colony-stimulating factor was found in the conditioned medium from erythroid cells. Thus, erythroid cells stimulated colony-forming activity of bone marrow cells, which was probably mediated via cytokine synthesis (e.g., granulocyte-macrophage colony-stimulating factor).

Animals↗

Characterization of erythroid cell-derived natural suppressor activity.

Nucleated erythroid cells (NEC) have been previously reported to the capable of suppressing antibody-mediated primary (IgM) and secondary (IgG) immune responses to thymus-dependent antigens. In the present study we indicated that NEC, separated from the spleens of mice following phenylhydrazine treatment were able to suppress directly the proliferative response of preactivated B cells to lipopolysaccharide (LPS) in vitro. While being active in suppressing B cell blastogenesis, NEC, however, failed to reduce both cell proliferation and cytotoxic T lymphocyte (CTL) generation in an allogeneic mixed lymphocyte culture (MLC). NEC also lacked a significant effect on interleukin (IL)-2 production and utilization by concanavalin A (Con A)-activated T lymphocytes. The NEC-derived suppression of B cell proliferation was, at least in part, mediated by soluble molecules. The specific blockade of transforming growth factor (TGF)-beta synthesis with antisense oligodeoxynucleotides (OD) binding TGF-beta mRNA, as well as the neutralization of TGF-beta activity with anti-TGF-beta antibodies (Ab), resulted in a detectable diminished ability of the NEC-conditioned medium (CM) to suppress B cell blastogenesis. Taken together, the results suggest that: 1) NEC may suppress directly B cell responses, while not affecting T cell ones; 2) NEC may mediate their natural suppressor (NS) activity partially through releasing TGF-beta.

Animals↗

Cytokine gene expression in erythroid cells.

Erythroid nuclear cells have been shown to exert regulatory effects on immunopoiesis. We have reported that some of these influences might be mediated via soluble factors secreted by nuclear erythroid cells. In this report we describe our estimate of the cytokine gene expression in cells isolated from individual erythroid colonies by Reverse transcription-Polymerase chain reaction. We found in erythroid cells, originated from the bone marrow precursors obtained from phenylhydrazine-treated mouse, the expression of the following cytokine genes: IL-1 alpha and IL-1 beta, IL-4, IL-6, GM-CSF, gamma-IFN and TGF-beta. In contrast, the erythroid cells derived from newborn mouse spleen precursor cells expressed IL-1 alpha, IL-1 beta, IL-4, IL-6 and GM-CSF mRNAs but not gamma-IFN and TGF-beta mRNAs. No detectable levels of IL-2, IL-3 and IL-5 mRNAs were expressed in nuclear erythroid cells. These data provide evidence of the expression of mRNAs coding in the set of immunoregulatory cytokines in immature erythroid progenitor cells in mouse.

Animals↗

[Level of Tx1- and Tx2-type cytokines in blood sera of hepatitis C patients].

The content of cytokines of type Tx1 (IL-2 and IFN-gamma) and type Tx2 (IL-4) in blood sera of 132 patients with hepatitis C and the combined form of hepatitis B + C was studied. For control, blood sera taken from healthy donors were used. A significant increase, in comparison with the control, in the content of IL-4 in all subgroups of the patients was registered. The content of IFN-gamma reached the maximum level in patients with acute hepatitis C with the positive result of the polymerase chain reaction (PCR) for the virus (216.4 and 46.4 pg/ml respectively) and was somewhat lower in acute hepatitis C with the negative PCR-result (77.7 and 9.6 pg/ml), mean while in the chronic course of hepatitis C these data were within the limits of control values irrespective of the results of PCR. In case of mixed infection in the acute clinical form a significant increase in the concentration of IFN-gamma (34.4 pg/ml) in comparison with the control (25.3 pg/ml) was observed. The content of IFN-gamma in patients with acute hepatitis C and the positive result of the test for NS antibodies also reached the maximum level (207.3 and 42.7 pg/mg respectively). But in contrast to hepatitis C in the acute form with the negative results of PCR in patients with hepatitis C in the acute form and the negative results of the NS test these data were within the limits of control values, as well as in the chronic course of hepatitis C irrespective of the results of the NS antibodies serum test. In case of mixed infection a significant increase in the concentration of IFN-gamma was registered in the subgroup of patients with the acute form of NS+ (39.9 pg/ml). The data obtained in this study were indicative of significant changes in the serum profile of serum cytokines of types Tx1 and Tx2 in different forms and courses of virus hepatitis. This makes it possible to believe that the chronization of the process was associated with the prevalence of the Tx2 function.

Adolescent↗

Production of cytokines by immature erythroid cells derived from human embryonic liver.

It is well known that regulatory interactions between hematopoietic and lymphoid cells are mediated by different mediators. The cells of erythroid lineage are not an exception and have a regulatory effect on hemato- and immunopoiesis that can be mediated through the production of cytokines i.e. by soluble factors - a universal mechanism for cell regulation in hematopoietic and immune systems. It has been previously shown that erythroid progenitor cells from mice express mRNA of cytokines such as IL-1 alpha and beta, IL-4, IL-6, IFN-gamma, GM-CSF and TGF-beta. In this report we present the results of the production of the main immunoregulatory cytokines by erythroid cells derived from human embryonic liver. It was revealed that the cell population enriched with erythroid progenitors, isolated from human fetal liver, can produce IL-1 beta, IL-2, IL-4, IL-6. The levels of production of cytokines by immature erythroid progenitor cells is compared to the levels of corresponding cytokines produced by mitogen-stimulated peripheral blood mononuclear cells. The production of these cytokines changed quantitatively under the effect of erythropoietin, and are correlated with the expression of differentiation markers of erythroid cells such as AG-EB and Glycophorin A. The role of cytokine production by erythroid cells in hemato- and immunopoiesis and the mechanisms of self-regulation of proliferation and differentiation of erythroid progenitor cells is discussed.

Cytokines↗

[Analysis of polymorphism of the interleukin-4 gene of healthy and HIV-infected persons].

The distribution of the allel variants of the promoter area (C = 590T) of the interleukin-4 (IL-4) gene in HIV-infected and relatively healthy representatives of the Caucasoid population has been studied. The relationship between the genotypes of this polymorphism and the production of IL-4 by mononuclear cells of peripheral blood as well as distribution of IL-4 genotypes among males and females is analyzed. The occurrence of the homozygous combination of the allel variant C/C of the promoter of IL-4 has been shown to prevail almost twofold over the occurrence of the variant C/T among healthy donors and HIV-infected patients. Sexual differences play an essential role in the character of inheriting the allel variants of the genes of IL-4, the presence of the homozygous variant C/C or T/T being a risk factor of HIV infection in males. As revealed in this study, in the peripheral blood of healthy donors mononuclear cells having genotype C/C differ from cells with the heterozygous variant C/T in higher spontaneous production of IL-4 and, simultaneously, in lower capacity for the activation of its production in response to stimulation with mitogen. In HIV-infected patients mononuclear cells differ in higher spontaneous production of IL-4 in comparison with controls. We may thus infer that the human genotype controlling the initial level of the production of IL-4 by lymphocytes Th2 may influence the intensity of antibody production in the process of infection.

Adolescent↗

[Lymphocyte subpopulations and level of the proinflammatory cytokines in the blood of patients with hepatitis C and with combined variant of hepatitis C and B].

Subpopulation of cytotoxic lymphocytes CD8 having both secretory and cytolytic antiviral activity is supposed to play the essential role in the virus elimination. Inflammatory reactions are also of importance in the hepatitis C pathogenesis, their intensity being regulated by anti-inflammatory cytokins. This study was aimed at determination of lymphocyte subpopulation indices--the relative content of cells carrying markers CD4, CD8, CD16, CD19, CD72, the parameters of the phagocytic activity of granulocytes and monocytes, as well as serum concentrations of anti-inflammatory cytokines IL-1, IL-6 and TNF-alpha. These indices were evaluated in a group 132 patients with confirmed hepatitis C or mixed hepatitis B + C diagnosis, depending on the disease form and markers of the infectious process activity (as determined in the PCR test for hepatitis C virus RNA) in comparison with a group of healthy donors. In patients with variant hepatitis under study a growth in anti-inflammatory mediators concentration was observed along with decreased indices of lymphocyte subpopulations responsible for cell-mediated immunity and the phagocytosis parameters. In the case of mixed hepatitis these differences were shown to be more manifested.

Antigens, CD↗

[Immunotropic properties of the causative agent of viral hepatitis C].

In this review the immunomodulating properties of the causative agent of viral hepatitis C are characterized on the basis of experimental data, obtained by Russian and foreign researchers during recent 3-5 years. The short characterization of the causative agent is presented and a number of adaptation mechanisms making it possible for hepatitis C virus to resist the action of the immune protective system of the host are considered. The role of individual protein products of the virus in the immunopathogenesis of the disease and the mechanisms of their action on the molecular level are discussed in detail on the basis of the results of mouse and in vitro experiments.

Animals↗

[The use of antisense oligonucleotides for modulation of cytokine gene expression].

The review summarizes literature data on the mechanism of action and the use of antisence oligonucleotides for modulation of cytokine gene expression in haemo- and immunopoesis. This new approach for gene-directed modulation of the gene expression allows to analyze both intercellular and intracellular protein interaction. Use of this approach is prospective for both experimental researches in vivo and in vitro and application in therapeutic purposes.

Animals↗