Immuno-pathomechanism of liver fibrosis: targeting chemokine CCL2-mediated HIV:HCV nexus
The aim of this study was to evaluate some patterns in expression of CC-chemokines (MIP-1alpha, MIP-1beta, MCP-1, RANTES) and their receptors (CCR1, CCR2, CCR3, CCR5) in peripheral blood leukocytes and liver biopsy samples from 21 patients with chronic hepatitis C. 10 healthy subjects were included in the control group. In patients with chronic HCV-infection significant increase of MCP-1 mRNA in liver tissue was observed as the disease progressed. Moreover, content of MCP-1 mRNA was significantly higher in liver as compared with blood. Level of MCP-1 mRNA in liver was directly related with histological changes. Levels of mRNA of CCR1, CCR2, CCR3, and CCR5 in blood of patients with minimal histological manifestations of chronic HCV-infection were significantly lower than in patients with more marked lesions. Expression of CCR1 and CCR5 mRNA in blood was directly correlated with histological activity index and degree of fibrosis. Conducted study demonstrates that progression of chronic hepatitis C is realized through local activation of MCP-1 mRNA synthesis leading to systemic response which manifested by increase of expression of CCR1, CCR2, CCR3, and CCR5 in peripheral blood leukocytes.