Effect Of Nucleoside Analogue On HBV Induced Chemokine MIG Expression

Objective To determine the alternation of MIG induced by HBV following nucleosideanalogues treatment, to investigate the contribution and significance of chemokine MIG in thedamage of liver tissue and cells during chronic hepatitis B virus infection.Methods Serum MIG level in patients with chronic hepatitis B (CHB) was detected byenzyme-linked immunosorbent assay (ELISA). Intrahepatic MIG and HBx expression inCHB patients was detected by immunohistochemistry. Further the change of serum MIG levelin32CHB patients before and after nucleoside analogues treatment for3months wasmeasured. The effect of lamivudine to MIG and HBx mRNA and protein expression inHepG2.2.15cells was examined by real-time PCR and Western blot, the change of HBV-DNAlevel was tested at the same time.Results Serum MIG level in CHB patients was significantly higher than that in healthycontrol (573.8/736.1vs.127.9/255.1pg/ml)(p<0.01). Serum MIG level in CHB patients waspositively correlated with serum HBV-DNA level(r=0.3092, p<0.01) and ALT level(r=0.3904,p<0.01), also correlated with liver nodule change and ascites and malignant transformation(p<0.05). The intrahepatic level of MIG protein in CHB patients is higher than control(p<0.05), the expression of MIG protein is correlated with HBx in CHB liver tissue(r=0.3923,p<0.05). The expression of MIG was strikingly reduced after nucleoside analogues treatment(613.6/246.7vs.789.0/337.3pg/ml)(p<0.05), accompanied by serum HBV-DNA and ALTlevel decreasing (p<0.01). The MIG and HBx mRNA and protein expression in HepG2.2.15cells was reduced by lamivudine (p<0.05), the extracellular HBV-DNAwas also inhibited.Conclusion Chronic HBV infection can induce chemokine MIG expression in liver cells andendothelial cells, MIG induce inflammatory cells migrating to focus of HBV infection, causedamge of liver cells and tissue. Nucleoside analogues can reduce MIG level throughinhibiting replication of hepatitis B virus and down regulating of HBx protein expression, thuslessen the damage of liver cells after chronic HBV infection, delay the development ofhepatitis B.