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PO1-4-35

A novel anti-inflammatory and immunomodulatory drug CP-25 alleviated collagen induced arthritis by down-regulating BAFF-NF-kapaB signaling pathway

[Speaker] Lingling Zhang:1
[Co-author] Jinling Shu:1, Xianzheng Zhang:1, Le Han:1, Wei Wei:1
1:Institute of Clinical Pharmacology, Anhui Medical University, China

Background B cell activating factor (BAFF) plays an important role in the differentiation, survival and activation of B cells rheumatoid arthritis (RA). BAFF receptor (BAFFR) is a crucial receptor for the survival of mature B cells in developing B cells. Paeoniflorin-6'-O-benzene sulfonate (CP-25) exerted its anti-inflammatory effects through regulating immune cells responses. The study was to investigate the regulatory effect of CP-25 on BAFF/BAFFR-nuclear factor of kappa B (NFkapaB) signaling in B cell of collagen induced-arthritis (CIA) mice.Methods Mice CIA was induced by injection of type II collagen. Arthritis index (AI) and swollen joint count (SJC) were assessed, spleen and joints histopathology were observed.B cells subsets, BAFF receptor were analyzed by flow cytometry. BAFF and immunoglobulin (Ig) levels were measured by protein antibody array. The expressions of TRAF2, MKK3, MKK6, p-P38, and p-NFkapaB65 in NF-kapaB signaling were analyzed by western blot.
Results CP-25 decreased AI and SJC, reduced thymus index and spleen index, inhibited T/B cells proliferation, alleviated spleen and joints histopathology. CP-25 also reduced high levels of serum BAFF and immunoglobulin, decreased CD19+ B cells, CD19+CD27+ B cells,and CD19-CD27+CD138+ plasma cells, inhibited BAFFR and TACI expressions, decreased the expressions of TRAF2,MKK3, MKK6, p-P38, and p-NFkapaB65. Compared with biological agents etanercept and rituximab, CP-25 restored high T cells proliferation and percentages of B subsets to normal level, and recovered high expressions molecules in NFkapaB signaling to normal levels. The action intensity of rituximab and etanercept was more strong than CP-25.
Conclusion CP-25 might be a promising anti-inflammatory immune and regulation drug, which alleviated CIA and regulated the functions of B cells through BAFF/BAFF receptor-NFkapaB signaling.
Key words: collagen induced-arthritis, B cell, BAFF, CP-25, comparison efficacy, biological agents
Foundation item: This work was financially supported through the National Natural Science Foundation of China (No. 81330081, 81473223 and 81673444).
Corresponding author: ZHANG Ling-ling, Tel: 13856001266, E-mail:llzhang@ahmu.edu.cn
 WEI Wei, Tel: 13605510563, E-mail: wwei@ahmu.edu.cn
Affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China

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