Vol 13, No 3 (2013)

Cytokines - family of polypeptide molecules, that are produced by tissue cells and regulate embryogenesis, some normal physiological functions, defense reactions to pathogens, and several pathological processes including immunopathology, carcinogenesis, heart and vascular pathology, etc. Different experiments led to conclusion that in case of hyperproduction cytokines instead of defense factors can become the mediators of pathology. During infections elevated cytokine synthesis followed with tissue inflammation depends on the pathogen associated molecular patterns binding to the pattern recognition innate immunity receptors. In non-infectious diseases like autoimmune, allergic, and other immunopathologic conditions cytokines also induce tissue inflammatory changes. In autoinflammatory diseases including metabolic syndrome elevated cytokine synthesis is due to endogenous danger molecules binding to pattern recognition receptors. In both cases cytokines can induce tissue and organ changes with the following development of the human disease clinical symptoms. Scientific studies in this field led to the so called cytokine theory of diseases, according to which cytokines are the main reason for pathology development. Due to this theory there are two principal variants of cytokine usage in clinical practice: cytokine therapy when recombinant cytokines are used to cure cytokine deficiency or their changed balance; and anticytokine therapy for inhibition of hyper produced endogenous cytokines.

Studying of thymic mast cells population in normal state and after stress-induced atrophy was a background of this work. Work is performed on 60 thymus of white outbred mice with using of histochemistry and immunohistochemistry methods. Adult mice were given a single injection of 2,5 mg of hydrocortisone for induction of thymic accidental transformation; sections were stained with toluidine blue and alcian blue-safranin. Immunohistochemical reactions for the synaptophysin or tyrosine hydroxylase with alcian blue stain were used for identification of nerve terminals in adult thymus. In adult animals MCs were observed only in the connective tissue of the capsule, interlobular septa, subcortex and perivascular space. Mast cells mature in thymus after accidental transformation. The localization of developing mast cells was changing from medullar and cortical to capsular. A morphological proximity between nerve terminals and mast cells have been observed in normal adult thymus. Some of these nerves are catecholaminergic. Possible important role of thymic mast cells and mast cells-nerves interaction in normal state and after accidental transformation is discussed.

We investigated the effect of overexpression of alpha-synuclein in the dopaminergic neurons on neurodegeneration and proinflammatory activation of microglial cells in the substantia nigra to test hypotheses about the relationship of neuroinflammation and neurodegeneration. The degree of neuroinflammation influence on neurodegeneration judged by the administration of corticosterone to rats with rAAV human alpha-synuclein. It has been found that the introduction of the vector dramatically reduces the number of dopaminergic neurons (-86,5+16,8%), while corticosterone injection significantly increased the number of surviving dopaminergic neurons in rats with rAAV human alpha-synuclein (+35,7+12,4%). Immunohistochemical study showed a increase in the expression of MHC II and IL-1 and the severity of gliosis. The findings suggest that there is neurodegenerative effect of elevated levels of endogenous alpha-synuclein, and its pro-inflammatory effect on microglia activation which, in turn, increases the intensity of neurodegeneration.

Follow-up clinical and immunological studies were undertaken to examine the CD28+ T-lymphocyte, CD40+ B-lymphocyte response in the sera of neonatal infants with cytomegalovirus infection. The pathogenetic role of anti-infective protection was established. The significant decrease in the levels of CD20 +CD40 + and lowering CD3 +CD20 + was found to be a prognostically poor determinant serios cytomegalovirus virus infection. It was revealed that for the preservation of neurological symptoms by the end of the first year of life it is statistically significant to determine in peripheral blood functional activity of CD3, CD4, CD40T-lympho-cytes, lymphocytes expressing CD28, CD3 -CD28+ in the total population, T-lymphocytes without CD28 (CD3+CD28 -) costimulation marker and also T-lymphocytes expressing CD71+, CD95+ markers of late activation on their surface.

Antibacterial peptides defensins display multifunctional activity. Our previous study revealed a modulating effect of rabbit and human (HNP-1) defensins on afferent synaptic transmission in the vestibular epithelium of the frog. The current study investigated the possible involvement of the opiate receptors in defensin modulation of glutamatergic synaptic transmission. Hair cell synaptic transmission was examined using the methods of electrophysiological recording of multiunit nerve fibers activity and externally applied drugs. Specific agonist μ-opioid receptor (OR) DAGO (0,1-100 μM) and specific agonist К-OR U-50448 (1 nM -10 μM) decreased the level of background discharge in the afferent fibers. The resting activity was increased during application of specific antagonist κ-OR nor-Binaltorphimine (nor-Bin) in concentration 0,01-10 μM. Specific antagonist Ц-OR CTAP (0,01-1 μM) provided two-phase positive-negative action. Application of specific agonist 5-OR DSLET (0,1-10 ЦМ) and antagonist δ-OR naltrindole (1 nm-10 μM) did not modify the resting activity. CTAP (100 nm) and nor-Bin (10 ЦМ) antagonized the depressive effect of HNP-1 (1 nm), supporting the evidence for competitive interaction of HNP-1 and μ- and κ-opioid receptor ligands. The results obtained suggest that the immune system can modulate afferent synaptic transmission of the vestibular epithelium of the frog. Cross talk between glutamatergic and immune system by means of μ-and κ-opiate receptor subtypes is discussed.

Streptococcus pyogenes is well-known human pathogen. The transcriptional regulatory protein Rgg controls the variety of S. pyogenes phenotypes, in particular, virulent phenotype. In this study the rgg gene was restored in SF370 rgg- и NZ131 rgg- mutant strains under native and plasmid heterologous promoters. Transcriptional level of rgg gene under the control of heterologous promoter was 2-fold higher than that under the control of native promoter. Restoration of rgg in the chromosome under the control of the native promoter restored wild-type phenotypes. In contrast, episomal complementation of rgg under plasmid heterologous promoter did not restore any of phenotypic properties. Together, the results indicate that the mechanism of Rgg-mediated regulation is complex. Given the importance of Rgg in controlling virulence properties in S. pyogenes, further characterization of the mechanism of Rgg-mediated gene transcription is necessary.