| BackgroundZinc (Zn) is a ubiquitous trace element. Zinc is an important component of more than 300 kinds of enzymes and transcription factors. It plays an important role in structure stable, catalytic and regulatory function. Worldwide, the incidence of diseases caused by zinc deficiency is estimated to more than 20%. Zinc deficiency may affect the health of more than two billion people in developing countries. Zinc deficiency occurs mainly due to malnutrition, aging, and inborn or acquired impairment of zinc uptake, and can lead to thymic atrophy, malfunction of immune cells, and subsequently, high incidence of infections, accompanied by growth retardation and endocrine dysfunction. In clinical practice, zinc supplementation may be one of the effective adjunctive treatments of diseases caused by zinc deficiency, especially vulnerable populations:children and the elderly.Zinc is essential in both cell-mediated and humoral immunity. Zinc deficiency results in a multitude of alterations in immune function, including impairment of cellular mediators of innate immunity. The immune system is regulated delicately by zinc homeostasis. The functions of zinc in the immune system have been studied extensively. Zinc homeostasis is highly regulated via the gastrointestinal tract. This tight regulation requires multiple transporters to work in coordination. Two families of mammalian zinc transporters exist:ZIP and ZnT. As the opposite zinc transporting function of the two zinc transport gene families, they play a crucial role in maintenance of both intracellular and extracellular zinc homeostasis. Over the last decades, epidemiological studies have associated reduced plasma/serum zinc levels with numerous medical conditions, such as diarrhea, pneumonia, diabetes mellitus, sickle cell anemia, impaired function of the immune system, gastrointestinal and chronic liver diseases and cancer.Due to the fact that CHB infected patients are unable to completely eradicate intercellular HBV from the hepatocytes, it seems that these patients may be functionally defective in some aspects of their immune system. Because of the important role that ZIP8 plays in the regulation of innate immunity, it may be speculated that the molecule is crucially important in the pathogenesis of CHB. Therefore, the main aim of this study was to investigate mRNA and protein expression levels of ZIP2 and ZIP8 in the PBMCs of CHB patientsZIP2 and ZIP8 belong to the ZIP family of metal-ion transporters. It can transport zinc. ZIP8 is closely related with inflammation and immunity. ZIP8 caused T cells to exhibit enhanced activation. Our lab found that ZIP2 over-expressed in leukocytes of asthmatic infants and pulmonary tuberculosis patients with lower serum zinc level. ObjectiveThe persistence of virus that resulted from the low antiviral immune response had been thought to contribute to the pathogenesis of Hepatitis B virus (HBV)-induced diseases. So we wondered whether ZIP2 and ZIP8 were changed in the patients with chronic hepatitis B patients (CHB) and chronic hepatitis C patients (CHC). We observed the expression of ZIP2 and ZIP8 in THP-1 after HBV treatment, while also detected the expression of IL-6 and TNF-α in THP-1 after HBV treatment. MethodsWe examined the mRNA and protein expression levels of ZIP2 and ZIP8 zinc transporters in peripheral blood mononuclear cells (PBMC) from patients with CHB (n=41), CHC (n=23) and healthy controls (n=39).THP-1 cells were induced into macrophage-like cells after PMA treatment. Macrophage-like cells were collected at24h and 48h after HBV treatment in order to test the expression of ZIP2 and ZIP8. ResultsBoth ZIP2 and ZIP8 mRNA levels as well as protein expression levels were significantly decreased in CHB and CHC patients compared with healthy controls. While ZIP2 and ZIP8 mRNA levels had no significant difference among CHB patients with different HBV-DNA copy numbers. ZIP2 and ZIP8 mRNA levels had no significant difference among CHC patients with different HCV-RNA copy numbers. The expression of ZIP2 and ZIP8 increased in THP-1 after HBV treatment. The expression of IL-6 increased in THP-1 after HBV treatment at 48h, while the expression TNF-a was down-regulated in THP-1 after HBV treatment at 48h. ConclusionThe results indicated that decreased expression of ZIP2 and ZIP8 genes are closely associated with immunity of CHB and CHC patients and suggest a role for ZIP2 and ZIP8 genes in the initial control infection and mediate the resistance and immunity of CHB and CHC patients through the promotion and maintenance immune response of adaptive T cell. |
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