Protective role and immunoregulatory effect of CXCR3 in hepatic ischemia- reperfusion injury

Objective To investigate the role and action mechanism of chemokine (C- X- C motif) receptor 3 (CXCR3) in hepatic ischemia- reperfusion injury (IRI) .Methods Forty- eight mice were divided into operation group and sham- operation group.The operation group was treated to establish a mouse model of IRI.Liver tissues were obtained at 3, 6, 12, and 24 h after IRI, with 6 mice at each time point.The expression of chemokine (C- X- C motif) ligand 9- 11 (CXCL9- 11) and their receptor CXCR3 were measured by real- time PCR and Western blot.The effect of CXCR3 was blocked by its specific antagonist C6.Hepatic injury was estimated based on the activity of hepatic transaminase and morphological indices.The distribution of subsets of infiltrating T cells was analyzed by flow cytometry.All data were expressed as mean ± standard deviation.Comparison between groups was made by one- way analysis of variance.Results Compared with the sham- operation group, the operation group had significantly upregulated expression of CXCL9- 11 and CXCR3 at all time points after IRI (P < 0.05) .Blocking CXCR3 significantly protected liver function and morphology (P < 0.05) .Antagonist C6 significantly reduced Th1 cell infiltration (P < 0.01) , but significantly increased Treg infiltration (P < 0.01) .Conclusion CXCR3 is an ideal therapeutic target in IRI treatment due to its relationship with immunoregulation.