CHEMOKINES AND THEIR RECEPTORS EXPRESSION IN BLOOD AND LIVER TISSUE IN CHRONIC HEPATITIS C

Abstract. Chronic hepatitis C (CHC) is widely spread disease with a long incubation period and weakle expressed clinical features. Pathogenesis of CHC despite of intensive efforts is still unclear. Due to scarcity of clinical signs diagnosis and monitoring of CHC represent considerable difficulties. Chemokines and chemokine receptors are fascinating object for investigation since they are mediators of chronic inflammation. Therefore, studying local and systemic immune response by evaluating expression of genes encoding chemokines and their receptors is of sufficient interest. In present study we investigated peripheral leukocytes samples and liver biopsies from 21 CHC patients. Blood leukocytes of 10 healthy volunteers were studied as a control for expression of mRNA for chemokines and their receptors. For all biopsies histological examination including evaluation of fibrosis and histological activity index was performed. mRNA’s encoding MIP-1α, MIP-1β, MCP-1, RANTES, CCR1, CCR2, CCR3, and CCR5 were under study. We found that the level of liver MCP-1 mRNA expression is increased reflecting degree of disease progression, moreover it was significantly higher in liver as compared with blood. The results of study showed that the changes in chemokine/receptor system in blood of CHC patients were significantly stronger as compared with intrahepatical expression of specific mRNA’s. The contents of CCR1, CCR2, CCR3, and CCR5 mRNA in patients with minimal histological manifestations were significantly lower than in group with more severe ones. CCR1 and CCR5 mRNA expression did directly correlate with histological activity index and fibrosis degree. The values MCP-1 mRNA’s in liver biopsies were in direct correlation with histological manifestations. In general, our study shows that CHC progression may be connected with local activation of MCP-1 gene thus leading to systemic response as increased expression of CCR1, CCR2, CCR3, and ССR5 genes in peripheral blood leukocytes.

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