Berberine Suppression of Human IgE but Not IgG Production via Inhibition of STAT6 Binding Activity at IgE Promoter by BCL6

IgE may lead to life-threatening anaphylaxis. Currently, no satisfactory treatment to inhibit IgE production exists. This study aims to explore the anti-IgE effect of berberine (BBR) and possible mechanisms using human tonsil cells. Tonsil cells were treated with BBR at different doses following stimulation with anti-CD40/IL4 alone or in combination with poly I:C and Pam3CSK4 for 10 or 4 days. IgE and IgG levels were determined by ELISA and cell viability by trypan blue exclusion. Gene expression was analyzed by qRT-PCR and affinity binding assay was performed by chromatin immunoprecipitation assay (ChIP). BBR showed dose-dependent inhibition of IgE production following anti-CD40/IL4 stimulation without affecting cell viability and IgG levels. BBR (10 µg/mL) completely inhibited IgE production by B cells stimulated with anti-CD40/IL4 in combination with vaccine adjuvants-poly I:C and Pam3CSK4 without affecting IgG levels and cell viability. BBR inhibited IgE heavy chain (IgEh), epsilon germline-transcript (εGLT), STAT6, and NFκB1 and enhanced IFN-γ, NFκB1A, and BCL6 gene expression. ChIP assay showed that BBR inhibited STAT6 binding in the IgEh promoter region by enhancing BCL6 binding. This study shows BBR regulates IgE in human tonsil cells by inhibiting STAT6 binding through BCL6 at the IgEh promoter showing its potential for treating IgE-mediated allergies.