Expression of CXC chemokine IP-10 in patients with chronic hepatitis B

BACKGROUND: Chemokines have strong chemoattractant effects and are involved in a variety of immune and inflammatory reactions, such as attracting activated T lymphocytes, neutrophils, monocytes and natural killer cells via the pathway of G protein-coupled receptors to sites of inflammatory injury and contribute to wound repair. This investigation was designed to assess the levels of chemokine interferon-gamma inducible protein-10 (IP-10) and IP-10 mRNA, and the relationship between IP-10 mRNA and HBV-DNA and alanine aminotransferase (ALT) in patients with chronic hepatitis B. METHODS: The levels of IP-10 mRNA in peripheral blood mononuclear cells (PBMCs) were kinetically detected by real-time polymerase chain reaction (PCR). The rate of chemokine/GAPDH was regarded as the extreme level of chemokine. The level of IP-10 in serum was measured by enzyme linked immunosorbent assay (ELISA), and the expression of IP-10 in hepatic biopsy tissue was detected by streptavidin-peroxidase (SP) immunohistochemistry. RESULTS: The level of IP-10 mRNA in the PBMCs of patients was 0.7387 +/- 0.0768 (lg cDNA/lg GAPDH); it was significantly higher in patients with chronic hepatitis B than that in normal controls (P<0.001). The level of IP-10 in the serum of patients was 660.9 +/- 75.5 pg/ml. There was a significant difference between patients with chronic hepatitis B and normal controls (P<0.05). In patients with chronic hepatitis B, the level of IP-10 mRNA in PBMCs was correlated with the IP-10 plasma level (r=0.7312, P<0.001), and the IP-10 plasma level was fairly correlated with the levels of ALT and HBV-DNA plasma (r=0.7235, P<0.001; r=0.7371, P<0.001). IP-10 was found by immunohistochemical analysis to be selectively upregulated on sinusoidal endothelium. CONCLUSIONS: The expression of IP-10 mRNA in PBMCs, IP-10 plasma concentration and the expression of IP-10 in sinusoidal endothelium are all high in patients with chronic hepatitis B. Chemokine IP-10 may play an important role in trafficking inflammatory cells to the local focus in the liver and induce the development of the chronicity of hepatitis B.

Relationship between the expression of IP-10 and IP-10 mRNA in peripheral blood and HBV DNA level in patients with cirrhosis

BACKGROUND: Post-hepatitic cirrhosis is regarded as common and severe form of liver damage. Interferon gamma-inducible protein 10 (IP-10), a member of the non-ELR (glutamic-leucine-arginine) motif CXC chemokine family, has recently been shown to recruit and activate specific subsets of leukocytes to sites of inflammation or an immune response during the development of hepatic cirrhosis. However, the effects of IP-10 and IP-10 mRNA on inflammatory infiltration at local sites and in the peripheral blood of patients with post-hepatitic cirrhosis as well as their relationship with viral load are still poorly defined. This study aimed to detect the relationship between the expression of IP-10 in serum, IP-10 mRNA in peripheral blood mononuclear cells (PBMCs), and the levels of HBV DNA in the serum of patients, and to explore their role in the pathogenesis of cirrhosis. METHODS: Typical patients with cirrhosis after HBV infection were selected, and their serum IP-10 concentrations were evaluated with ELISA, the content of IP-10 mRNA in PBMCs was measured by real-time PCR, and the load of HBV DNA in serum and PBMCs was assessed by semi-quantitative analysis of gel imaging. RESULTS: The levels of IP-10 in serum and IP-10 mRNA in PBMCs of patients with cirrhosis were 299.9 +/- 77.2 pg/ml and 0.7500 +/- 0.1495, respectively. They were higher than those of controls (P<0.05) and also increased in the HBV DNA(+) groups (P<0.05, P<0.01) to 343.0 +/- 80.3 pg/ml and 0.8465 +/- 0.1528, respectively. The levels of IP-10 in serum and IP-10 mRNA in PBMCs were clearly correlated with the load of HBV DNA (P<0.01). CONCLUSIONS: The levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis increase are closely correlated with the load of HBV DNA in serum, and play a key role in the progression of post-hepatitic cirrhosis. (Hepatobiliary Pancreat Dis Int 2010; 9: 280-286)