| Objective: To investigate the expression of CXC chemokine receptor (CXCR1, CXCR2) and their common ligand IL-8in the peripheral blood and liver biopsy tissue of the patients with cirrhosis, and the role of CXCR1, CXCR2and IL-8on regulation of proinflammation molecular mechanism of cirrhosis.Methods:Real-time PCR was used to examine the mRNA expression of chemokine receptor CXCR1and CXCR2and their ligand IL-8in the peripheral blood of sixty-five cirrhosis (compensated cirrhosis36, decompensated cirrhosis29). The levels of IL-8in serum were detected by ELISA. Further observation of their mRNA was analyzed before and after the IFN therapy for three months, six months and one year. The ratio of logcDNA/logGAPDH was regarded as the extreme level of CXCR1, CXCR2, IL-8mRNA. The expression of CXCR1, CXCR2and IL-8in liver biopsy tissue was detected by SP immunohistochemistry stain.Results:The mRNA of CXCR1and IL-8in the PBMCs (0.6925±0.1354,1.4850±0.1801logcDNA/logGAPDH) were significantly higher than those in controls (P<0.01), so was the level of IL-8in serum (P<0.01). The CXCR2mRNA expression in cirrhosis (0.4344±0.0694logcDNA/logGAPDH) was lower than that in normal controls, but there was no significant difference between the two groups (P>0.05). The levels of CXCRl, IL-8mRNA and IL-8were significantly higher in decompensated cirrhosis (0.7662±0.1292,1.5453±0.1783,488.19±49.44pg/ml) than those in compensated cirrhosis (P<0.05, P<0.01), and there were also obviously divergences between in positive of HBVDNA (0.7498±0.1106,1.5676±0.1558,472.21±52.41pg/ml) and in negative of HBVDNA (P<0.01). The CXCR2mRNA expression in decompensated cirrhosis (0.4279±0.0732) was lower than that in compensated cirrhosis (0.4397±0.0668), but there was few significant differences between the two groups (P>0.05). The viral loads in the PBMCs and serum of seventeen compensated cirrhosis before treatment of IFN were10(5.07±0.80) copies/ml,10(5.93±0.78) copies/ml, and the levels of ALT, AST were (84.41±30.65)U/L,(72.29±35.69)U/L, and the expression of CXCR1, CXCR2, IL-8mRNA were (0.7089±0.0713),(0.4532±0.0527),(1.5243±0.1541) logcDNA/logGAPDH, and the level of IL-8in serum was (440.58±36.63)pg/ml. After treatment for three months, the viral loads were down regulated to10(4.58±0.87) copies/ml、10(5.18±0.81) copies/ml, and the levels of ALT and AST were (96.71±25.41)U/L,(84.76±26.76)U/L, which were both higher than those of before treatment. The levels of CXCR1, CXCR2and IL-8mRNA were (0.6557±0.0916),(0.4293±0.0634),(1.4745±0.1398) logcDNA/logGAPDH, few difference was explored (P>0.05). However, the level of IL-8in serum was (395.99±32.56)pg/ml, which had more evidently difference compared with before treatment (P<0.01). After treatment for six months, the levels of viral loads, ALT, AST, IL-8in serum, CXCR1, CXCR2and IL-8mRNA were further decreased to100(2.91±0.75) copies/ml,10(3.08±0.76) copies/ml,(62.06±17.75)U/L,(53.94±22.00)U/L,(281.93±33.83)pg/ml,(0.5203±0.0876),(0.4122±0.0557),(1.2961±0.1363) logcDNA/logGAPDH, which were obviously lower than those in controls (P<0.05, P<0.01). After treatment for twelve months, the levels of viral loads, ALT, AST, IL-8in serum, CXCR1, CXCR2and IL-8mRNA were10(2.29±0.86) copies/ml,10(2.11±0.67) copies/ml,(38.82±11.81)U/L,(36.53±12.58)U/L,(188.11±31.78)pg/ml,(0.4246±0.0799),(0.4034±0.0522),(1.1570±0.1385) logcDNA/logGAPDH, respectively. The total mRNA levels of CXCR1, CXCR2, IL-8and viral loads, ALT, AST, IL-8in serum all obviously decreased (P<0.01). The CXCR1mRNA expression was obviously correlated with the levels of ALT (r=0.687, P<0.01) and AST (r=0.601, P<0.01) in cirrhosis. However, the CXCR2mRNA expression was no correlated with the level of ALT (r=0.143, P>0.05) and AST (r=0.196, P>0.05) in cirrhosis. IL-8mRNA expression was apparently correlated with the levels of ALT (r=0.612, P<0.01) and AST (r=0.579, P<0.01) in hepatitis B-related cirrhosis. Moreover, SP immunohistochemistry stain displayed that the expression of CXCR1and its ligand IL-8in liver biopsy of patients with cirrhosis were obviously upregulated than those in normal liver (P<0.05), while the expression of CXCR2was faint in liver biopsy of patients with cirrhosis, the difference has no statistically significant compared with normal liver. CXCR1, CXCR2and IL-8distributed in the liver cells, the inflammatory cells, and the endothelial cells and so on.Conclusions:The levels of CXCR1, IL-8and their mRNA increase in peripheral blood and liver biopsy tissue of the patients with cirrhosis, and have close correlation with the duplication of HBV-DNA and the levels of ALT and AST in serum, while the expression CXCR2and its mRNA has no significant rise in peripheral blood and liver biopsy tissue of the patients with cirrhosis, which suggests that CXCR1and its ligand IL-8, but not CXCR2, may mainly participate in the occurrence and development of cirrhosis.The excessive immune response to host can be induced during the early treatment of IFN, such as short-term of high levels of ALT, AST in the initial three months. IFN has significant better effects via the pathway of anti-viral and bidirectional immune regulation effects, and also can down-regulate the inflammatory response caused by over expression of CXCR1and IL-8.Figure [34] Table [8] Reference [104]... |
PDF Full Text Request