ABSTRACT
Objective To generate an primary biliary cirrhosis animal model and investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC).Methods Female C57BL/6 wild-type(WT)mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 consecutive weeks.Establishment of PBC was confirmed by liver function test,serom autoantibodies and liver biopsy.Expression of CXCR3 on lymphocytes of liver/spleen and level of CXCL10 in peripheral blood were tested by flow cytometry assay and ELISA.The t-test was used for two group data comparison.Results Anti-mitochondrial antibody was detected in the sera of all poly I:C injected wild type C57BL/6mice.Considerable numbers of inflammatory cells were detected at the portal areas 8 weeks after the initiation of poly I:C injection,which progressed up to 24 weeks.Compared the to control mice,serum level of CXCL10was increased in PBC mice.With the disease progression,CXCL10 serum level was elevated.The level of CXCL10 at 8,16 and 24 weeks in PBC model was 0.28±0.10,0.33±0.19 and 0.27±0.11,which were much higher than those of the control mice.CXCL10 serum level of control mice was 0.07±0.03.0.08±0.05,0.10±0.04 respectively.Compared to control model,the proportion of CXCR3+ positive cells was inereased in the intrahepatic infiltrates of PBC model,mostly on CD8+ T cells.Moreover,the expression of CXCR3 was decreased in CD3+and CD8+splenocytes from PBC model compared with control model.Conclusion CXCR3and CXCL1O may attract T cells to the liver of PBC mice mode in the process of PBC development