The Role Of STAT6 And NF-?B Signaling Pathway In The Production Of Immunoglobulin E In U266 Cell Line

Background and Purpose: In recent years,the incidence of allergic diseases has been getting higher and higher,causing the attention of Western countries and the world.However,there is nodefinite cure for the treatment of such diseases,but only to control the symptom of the disease.In the allergic disorders,immunoglobulin E(Ig E)mainly mediates type I hypersensitivity.Nowadays,the anti-allergy treatments we used were aimed to reduce the concentration of the free immunoglobulin E(Ig E)in the serum.For instance,omalizumab,which could treat the allergic diseases,binding to the free immunoglobulin E(Ig E),blocked the combination between the Ig E and the mast cells and eosinophil,thereby inhibiting the activation of the hypertrophy cell and eosinophil,reducing and preventing the release of the inflammatory mediators.However,these could not reduce the production of the immunoglobulin E(Ig E)fundamentally.Therefore,understanding the signal pathway of Ig E may provide new targets and ideas for the treatment of allergic diseases.Previous studies have shown that IL-4 and CD40 are essential in the production of Ig E.However,in the present study,the study of signaling pathways in Ig E production in B cell lines is rarely reported.On the basis of this study,two kinds of specific signal pathway inhibitors were used to understand the regulation of signal pathway by immunoglobulin E(Ig E)in B cell lines,and to provide new ideas and directions for the treatment of disease.Methods: B cell lines were induced with different concentrations of interleukin 4(IL-4)or different concentrations of anti-CD40 antibody(CD40),and the concentration of immunoglobulin E(Ig E)in the supernatant was determined by enzyme-linked immunosorbent assay(ELISA).And also,detected the changes of the heavy chain genes(?GLT)by q-RTPCR,by which we chose the optimal concentration of the interleukin4(IL-4)and the anti-CD40 antibody(CD40).The effects of two kinds of inhibitors on cell viability were measured by CCK8 cell proliferation and toxicity test.The appropriate concentration of inhibitor was selected.Using STAT6 specific inhibitors(A177-1726)and the NF-kappa B specific inhibitors(JSH-23)inhibited the two signaling pathways,immunoglobulin E(Ig E)in supernatant and Ig E heavy chain gene(epsilon GLT),as well as some changes in protein were detected.Results:(1)Different concentrations of IL-4 or CD40 can induce B cell lines to produce immunoglobulin E(Ig E)and can observe the expression of Ig E heavy chain gene changes;(2)The use of NF-KB-specific inhibitor JSH-23 inhibits the pathway,can clearly observe the reduction of immunoglobulin E expression level,and Ig E heavy chain gene expression changes;(3)Similarly,the use of STAT6-specific inhibitors,the concentration of immunoglobulin E and the expression of heavy chain genes were reduced.Conclusion: The results of this study indicate that NF-?B and STAT6 signaling pathways play an important role in the production of immunoglobulin E(Ig E)in B cell lines,Which can lay a theoretical foundation for clinical treatment of allergic diseases and provide reference value for finding therapeutic target.