Shuang-Huang-Lian prevents basophilic granulocyte activation to suppress Th2 immunity

BACKGROUND: Basophilic granulocytes (BGs) not only initiate the induction of Th2 cell differentiation, but also amplify the ongoing Th2 response. Shuang-Huang-Lian (SHL) is clinically used for relieving type I hypersensitivity by continuous treatment for several weeks. METHODS: ELISA, flow cytometry, magnetic activated cell sorting, isoelectric precipitation, hybridoma technique, transfection and luciferase reporter assay were used in this study. The statistical analysis was performed using a one-way ANOVA. RESULTS: Our recently published study demonstrated that SHL exerted a remarkable effect on mast cell stabilization. Herein, we sought to elucidate the effect of SHL on shrimp tropomyosin (ST)-induced Th2 immunity and its underlying mechanisms. The obtained data showed that continuous treatment with SHL significantly suppressed ST-stimulated Th2-cytokines release and IgE synthesis. A mechanistic study indicated that SHL not only reduced BG early IL-4 release before ST-specific IgE (sIgE) production, but also inhibited BG activation in the presence of sIgE, including suppressing CD200R surface expression and decreasing IL-4 production. Moreover, SHL markedly decreased the cytosolic Ca(2+) (Ca(2+)([c])) level and inhibited the nuclear factor of activated T cells (NFAT) activation in RBL-2H3 cells. CONCLUSIONS: Collectively, SHL potently reduces ST-induced Th2 immunity by inhibiting the BG Ca(2+)-NFAT pathway and, thus, suppressing the early IL-4 release before sIgE synthesis and inhibiting BG activation in the presence of sIgE. This study provides the pharmacological basis for the clinical use of SHL to relieve type I hypersensitivity by a successive dose regimen. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12906-017-2071-y) contains supplementary material, which is available to authorized users.