| The importance of IFN-γ pathways in host defense against intracellular pathogens was initially made clear through the experimental study of knockout mice. IFN-γ is synthesized only by certain cells of the immune system including natural killer cells (NK), CD4 Thl cells, and CD8 cytotoxic suppressor cells. IFN-γ plays an important role in innate and adaptive immunity. It stimulates specific cytotoxic immunity based on the recognition of cell surface-bound viral antigens expressed in association with major histocompatibility complex (MHC) proteins; and it activates macrophages. These immune responses play an important role in the anti-viral and anti-microbial actions of IFN-y. In addition, IFN-γ affects the differentiation of native T cells into either Thl or Th2 cells. IFN-γ possesses unique immunoregu-latory functions that are especially important in mediating protection against viral infections, especially long-term control of viral infections. Furthermore, in recent years, it has been demonstrated that T cells use IFN-γ to mediate non-cytolytic clearance of some viruses. Study of the IFN-γ system shed more light on the mechanism of pathogenesis and viral clearance, which is very important inviral hepatitis.IFN-γ exerts its actions through cognate cell surface receptors that are largely species-specific. The a chain receptor (IFNGR1) is a high affinity receptor that binds to IFN-γ in a symmetric bivalent manner to form a stable complex, which forms a binding template for the subsequent binding of two copies of the second receptor, IFNGRB This interaction causes the activation of kinases, then phosphorylation of the substrate proteins called STATs. The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcriptional activation of previously quiescent genes, take effect. IFNGRa is the gateway in this signal transduction pathway and its expression and functional status decide the effect of IFN-γ. In the past several years, mutations in the different genes in the IFNGRa, IL-12Rpl and IL-12p40 have been recognized. These mutations are associated with heightened susceptibility to diseases caused by intracellular pathogens including some bacteria and viruses, especially in the IFNGR deficiency.ObjectiveTo study the possible differences in the interferon gamma receptor (IFN-γR) response among a variety of clinical types in patients with chronic hepatitis B(CHB) and implications in pathogenesis.MethodsThe serum levels of IFN-γ and expression of IFN-γ Rl of in peripheral leucocytes, from 53 CHB patients were examined by ELISA and flow cytometry respectively, which were compared with the baseline levels of 15 healthy controls and were performed correlation analysis with ALT, TBil. HBeAg, HBV DNA load in serum and morphological change in hepatic tissues.ResultsThe results showed that IFN r Rl levels on membranes of lymphocyte in CHB patients, which positively correlated with liver inflammation(r=0.621, P<0.01) and serumTBlL(r=0.575,p<0.01),also negatively with HBeAg(r=-0.589,p<0.01), HBV DNA load (r=-0.714,p<0.01) , is much higher than the healthy controls(p<0.05),and no obvious difference on the membranes of monocytes, The serum levels of IFN-γ in patients with cirrhosis and severe hepatitis were higher than healthy controls(p<0.05),and the two was no difference from each other, but the standard deviation in each group was relatively large.ConclusionThese findings suggest that the IFN-γ signal transduction pathway is modulated through up-regulating the expression of IFN- r Rl on the membrances of lymphocytes, which partly takes part in the immuno-pathogenesis and Inhibition of hepatitis B virus replication in CHB patients. |
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