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

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).

• Authors: Ran Guo, Jun Li, Yufan Gu, Yunqian Li, Shanshan Li, Xiaoli Gao, Zhixiang Zhu, Pengfei Tu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 67 Pg. 473-482 (Feb 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30597293 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies
• B-Cell Activating Factor
• CD40 Antigens
• Chromones
• Immunoglobulin M
• Tnfsf13b protein, mouse
• Interleukin-4

Topics

• Animals
• Antibodies
• B-Cell Activating Factor (genetics, metabolism)
• B-Lymphocytes (drug effects)
• CD40 Antigens (immunology)
• Cell Proliferation (drug effects)
• Chromones (chemistry, pharmacology)
• Immunoglobulin M (immunology)
• Interleukin-4 (immunology)
• Male
• Mice
• Signal Transduction (drug effects)