[Regulation of the genes expression of CD4+ T-lymphocytes differentiation transcription factors by galectin-3 in vitro].

Now a number of CD4+ T-lymphocytes, known as Th1, Th2, Treg and Th17, is currently identified and well- studied. The methods basing on the targeted regulation of differentiation process of the Th-lymphocytes that carry out the immune response polarization attract an attention of scientists dealing with a correction of immune-mediated. In the present study, endogenous beta-galactoside-binding protein of the lectin family, galectin-3, was investigated as a regulator of T-cell homeostasis. A galectin-3 is known to be actively produced by tumor cells in malignant transformation and able to influence the processes of signal transduction, cell-cell cooperation and the implementation of programmed death. As cell differentiation processes are directly connected with the regulation of gene expression, we investigated the effect of recombinant galectin-3 on expression of mRNA of transcription.factors, which guide the differentiation of CD4+ lymphocytes. The study was performed on peripheral blood mononuclear cells of healthy individuals. The gene expression levels were evaluated by a real-time PCR. In the experiments in vitro, it has been first found the recombinant galectin-3 (0.5 mg/mL) up-regulating the expression of transcription factors Gata-3 and Rorc mRNAs and down-regulating the mRNA expression of transcription factors T-bet and FoxP3. Up to a concentration of 1 mg/mL recombinant galectin-3 stimulates Th-cells by dose-dependent manner, whereas at higher concentrations stimulating effect weakens, and inhibiting action starts prevailing. Thus, one can suppose that galectin-3 through regulation of lymphocytes differentiation promote development of allergic, autoimmune and neoplastic diseases that allows us to consider the galectin-3 as a.potential target for therapy of these diseases.

[Heat shock protein 90--modulator of TNFalpha-induced apoptosis of Jurkat tumor cells].

rTNFalpha-induced programmed death of Jurkat tumor cells cultured with 17-AAG, a selective inhibitor of heat shock protein (Hsp90), was studied by fluorescent microscopy with the use of FITC-labeled annexin V and propidium iodide. Caspase-3 and -8 activities were determined by spectrophotometry using a caspase- 3 and -8 colorimetric assay kit. It was shown that inhibition of Hsp90 leads to activation of Jurkat cell apoptosis while Hsp90 itself suppresses this process. 17-AAG enhances rTNFa-induced apoptosis of tumor cells.