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GYF-21, an epoxide 2‑(2‑phenethyl)‑chromone derivative, suppresses dysfunction of B cells mainly via inhibiting BAFF activated signaling pathways.

Ran Guo,Jun Li,Yufan Gu,Yunqian Li,Shanshan Li,Xiaoli Gao,Zhixiang Zhu,P. Tu

Published 2019 in International Immunopharmacology

ABSTRACT

Activated B cells targeted to autoantigens proliferate and differentiate into antibody-secreting cells. Overproduced autoantibodies will give rise to autoimmune diseases. In this study, we investigated the inhibitory effects of GYF-21, an epoxide 2‑(2‑phenethyl)‑chromone derivative extracted from Chinese agarwood, on the survival, activation, proliferation, and differentiation of B cells for revealing its potential to treat autoimmune diseases related to B cell dysfunction. The results showed that GYF-21 slightly inhibited the survival, activation and proliferation of B cells stimulated by combination of anti-IgM, anti-CD40 and IL-4 while weakly up-regulated differentiation of B cells induced by combination of anti-CD40 and IL-4. In addition, GYF-21 intensively suppressed survival, activation, proliferation, and differentiation of B cells stimulated by B-cell activating factor (BAFF) which plays extremely important roles in autoantibody production and pathogenesis of autoimmune diseases. The mechanism study revealed that GYF-21 slightly down-regulated phosphorylation of NF-κB p65, Akt, STAT3, but up-regulated phosphorylation of Erk1/2 in B cells activated by anti-IgM, anti-CD40, IL-4 or their combinations. However, GYF-21 not only moderately down-regulated phosphorylation of NF-κB p65 and MAPK p38, but also intensively inhibited phosphorylation of Erk1/2 and Akt induced by BAFF. These data suggest the inhibitory effects of GYF-21 on the survival, activation, proliferation, and differentiation of B cells mainly via blocking BAFF activated signaling pathways, and its potential to be developed into therapeutic drug for autoimmune diseases, especially systemic lupus erythematosus (SLE).

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