BAFF Promotes FLS Activation Through BAFFR-Mediated Non-canonical NF-κB Pathway and the Effects of CP-25

• Published in: Inflammation 2023-06, Vol.46 (3), p.861-875
• Main Authors: Wang, Han, Mei, Dan, Liang, Fa-qin, Xue, Zi-yang, Wang, Pan, Liu, Rui-jin, Zhao, Yu-chen, Jin, Lin, Zhang, Zi-wei, Zhai, Yuan-fang, Zhang, Xian-zheng, Wei, Wei, Zhang, Ling-ling
• Format: Article
• Language: English
• Subjects: Animals; Arthritis; Arthritis, Rheumatoid - metabolism; B-Cell Activating Factor - metabolism; B-Cell Activating Factor - pharmacology; B-Cell Activating Factor - therapeutic use; Biomedical and Life Sciences; Biomedicine; BLyS protein; Cell activation; Cell Proliferation; Cells, Cultured; Collagen; Drug development; Fibroblasts - metabolism; Immunology; Internal Medicine; Lymphocytes B; Mice; NF-kappa B - metabolism; NF-κB protein; Original Article; Osteoarthritis; Pathology; Pharmacology/Toxicology; Rats; Rheumatoid arthritis; Rheumatology; Signal Transduction; siRNA; Synovial Membrane - metabolism; Synoviocytes - metabolism; TRAF2 protein
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-022-01774-2

B cell activating factor (BAFF) has been shown to play a key role in regulating B cell function, but little is known about whether BAFF affects the function of fibroblast-like synoviocyte (FLS), an effector cell of rheumatoid arthritis (RA). CP-25, a new ester derivative of paeoniflorin, could alleviate the arthritis symptoms of collagen-induced arthritis (CIA) mice by inhibiting BAFF-mediated abnormal activation of B cells. In this study, we aimed to understand the mechanism by which BAFF activates FLS and the effect of CP-25 on FLS function. Therefore, the proliferation and migration abilities of FLS and key proteins on the non-canonical NF-κB pathway were examined. The results showed that compared with the FLS of normal rats/OA patients, the expression of BAFF-R, TRAF2, NIK, p-IKKα, P100, and P52 was higher in the FLS of AA rats/RA patients, while the expression of TRAF3 was lower. And, BAFF promotes FLS activation by activating the non-canonical NF-κB signaling pathway. Meanwhile, BAFFR-siRNA inhibited the proliferation of FLS and the activation of non-canonical NF-κB signaling in FLS induced by BAFF. Additionally, CP-25 could inhibit abnormal proliferation and migration of FLS by regulating non-canonical NF-κB signaling. We concluded that BAFF may act as an important role in facilitating the function of FLS through the BAFFR-mediated non-canonical NF-κB pathway, which would be useful for revealing the pathological mechanism of RA. And CP-25 may become a potential new drug for the treatment of RA, providing a scientific basis for the development of new drugs to treat RA.