Paper Title
Expression Activity of Genes Encoding Proteins - Inflammatory Regulators Decreases, As Affected By Metal Compounds, and Contributes to Prolonged Inflammation in Rats

Abstract
Rapid development of research in the field of immunology has led to many scientific breakthroughs; nonetheless, some aspects of immune-associate diseases remain under-explored. The most promising approach is based on the research of transcriptome of tissue-specific cells, which will highlight the genes responsible for varying degree of activation of the immune system. The goal of research was studying the expression of tissue-specific genes in thymus samples of rats with aseptic inflammation, previously seeded with vanadium and chromium compounds. All experiments were approved by the ethical committee of KazNMU named after S.D. Aspendiyarov (Record of proceedings No. 3 of 1/4/2015). The research was carried out on not pedigree male rats weighing 180-220 grams, contained under standard vivarium conditions on a standard dietary intake. Animals were randomly divided into 4 groups of 6 animals each: control animals; the animals with aseptic inflammation (AI); the animals which had been orally fed on ammonium vanadate and potassium bichromate in a dose of 5 mg / kg bwt. (Me); the animals among which, as seeding with metal compounds was over, aseptic inflammation was modeled (AI + Me). The control group of animals received a volume of physiological saline equivalent to solutions of metals. With the purpose of modeling aseptic inflammation, the rats were anaesthetized with chloroform, the interscapular region was shaved and cleaned with 70% ethanol, then 0.3 ml of turpentine oil was subdermally injected. In 24 hours after the modeling of aseptic inflammation, blood was sampled under chloroform anesthesia in animals of all groups under chloroform anesthesia, blood was collected, after euthanasia, the thymus was removed for sequencing. Bioinformatic analysis was performed using the following software packages: STAR, RSEM, IGV, DESeq2, MsigDB with GSEA software. Due to the analysis, made within the scope of metabolic and signaling pathways, in which the identified genes found in rat thymus samples were involved, significant changes in the functioning of innate and adaptive immunity were revealed. Comparing the groups AI and AI + Me was of the utmost interest for us. Genes that stimulate the immune system, having UPREGULATED signs, are involved in only three metabolic and signaling pathways (“GO biological process” and “Canonical pathways”). Overlapping of 140, 91 and 61 genes from both compared groups was observed. Genes with traits of “DOWNREGULATED” were found in 8 metabolic and signaling pathways (“GO biological process”), in 4 pathways from Hallmark base, in 9 pathways from the base of Canonical pathways. Low expression of these genes violated phagocytic activity of macrophages, B-cell immunity, cytokine signaling, regulation of STAT5 and NF-kB, which as you know, regulate bone marrow hematopoiesis and are known as suppliers of cells of the first line of defense in inflammation. As a result of visualization of differential expression of genes in the genomic browser, we have had a chance to identify a statistically significant Up-Down expression of 20 genes. The researches carried out allowed us to make the conclusion: differential expression analysis shows most pronounced effects in thymus, and little systematic effect in other tissues; In thymus, cell cycle genes are systematically upregulated upon treatment with metals; metals also show immune -suppressive effect, with many immune-related pathways going down; the immunosuppressive effect appears to be selective to B-cells.