The Immunomodulation Effect Of Huaier Aqueous Extract In Lymphoma Cells

Lymphoma is a kind of malignant tumor,which is involved in the patient's whole body tissues and organs with the symptoms of fever,night sweats and emaciation.It was reported that immune factors and physical factors are related with the lymphoma pathogenesis,but the specific mechanism for lymphoma pathogenesis remains ambiguous.Herein,in this paper,immunomodulation effect of Huaier aqueous extract on lymphoma U937 cells was preliminarily explored,and the development of lymphoma was further studied based on CD4~+CD25~+Treg cells,which can offer a theoretical basis in the clinical treatment of lymphoma.Firstly,we adopted lymphoma U937 cells induced mice as the experiment model.The preliminary immunomodulation effect was explored by testing lung,liver,kidney and cytokines.Results demonstrated that pretreatment of Huaier aqueous extract can relieve the injury of lung,liver and kidney tissue in the lymphoma mice and also can reduce the ability of secreting the cytokines of T_H1 and T_H2 cells.Moreover,the therapeutic effect of Huaier aqueous extract was more significant than that of Prednisone acetate tablets.Secondly,in order to explore the immunomodulation effect of Huaier aqueous extract on lymphoma U937 cells,the cytotoxity of Huaier aqueous extract to the lymphoma U937 cells was studied.The results showed that Huaier aqueous extract had an inhibitory effect on lymphoma U937 cells.IFN-?and IL-10 were analyzed through the transcriptional level and the results showed that the mRNA expression level of both cytokines were dependent on the concentration of Huaier aqueous extract.In order to further prove the conclusion,we analyzed intracellular proteins by an ELISA method,the results showed that the treatment group had the higher expression level of IFN-?and lower expression level of IL-10,indicating Huaier aqueous extract exerted influence on the expression levels of IL-10 and IFN-?in U937 cells.On the other hand,mitochondria are the control center of the interferon regulation,the integrity of mitochondria directly affected the secretion of inflammatory cytokines.Results showed that the integrity of mitochondria was destructive with the increasing concentration of Huaier aqueous extract.Lastly,in order to explore the specific mechanism for lymphoma pathogenesis,we focused on CD4~+CD25~+Treg cells.In this experiment,we used A20 cells induced transplanted tumor model for describing the function of Treg cells and exploring the role of Treg cells.In model groups,IL-6 and IL-10 expressed higher levels,which implied CD4~+CD25~+Treg cells can up-regulate the expression of IL-10 and IL-6.Foxp3,as an auxiliary marker of CD4~+CD25~+Treg cells,was verified to have the increased expression in the model group.Through magnetic bead screening,we found that the contents of CD4~+CD25~+Treg cells in the thymus and liver were increased and in peripheral blood and spleen were significantly decreased,suggesting that the decrease of CD4~+CD25~+Treg cells in peripheral blood and spleen could lead to lymphoma.In summary,results showed that the therapeutic effect of Huaier aqueous extract was more significant than that of Prednisone acetate tablets.Huaier aqueous extract can inhibit the proliferation of lymphoma U937 cells,and increase the number of CD4~+CD25~+Treg cells of peripheral blood and spleen,and decrease the number of CD4~+CD25~+Treg cells of liver and thymus,which indicated that CD4~+CD25~+Treg cells are closely related to the growth and proliferation of lymphoma.These results suggested that Huaier aqueous extract can inhibit the occurrence and development of lymphoma,which provides a better basis for the treatment of lymphoma.