A novel anti-inflammatory and immunomodulatory drug CP-25 alleviated collagen induced arthritis by down-regulating BAFF-NF-κB signaling pathway
10.3867/j.issn.1000-3002.2017.10.039
- Author:
SHU JIN-LING
1
;
ZHANG XIAN-ZHENG
;
HAN LE
;
ZHANG FENG
;
WU YU-JING
;
Tang XIAO-YU
;
WANG CHEN
;
TAI YU
;
WANG QING-TONG
Author Information
1. Institute of Clinical Pharmacology
- Keywords:
collagen induced- arthritis;
B cell;
BAFF;
CP- 25;
comparison efficacy;
biological agents
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(10):969-970
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigated the regulatory effect of paeoniflorin-6'-O-benzene sulfonate (CP-25) on B cell activating factor (BAFF)/BAFF receptor-nuclear factor of kappa B (NF-κB) signaling in B cell of collagen induced-arthritis (CIA) mice. METHODS Mice CIA was induced by injection of typeⅡcollagen (CⅡ). The arthritis index (AI) and swollen joint count (SJC) were assessed, and histopathology of spleen and joints were observed. The percentage of B cells subsets, BAFF receptor expressions 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-NF-κB65 in NF-κB signaling mediated by BAFF were analyzed by western blot. RESULTS CP-25 decreased AI and SJC, restored abnormal weights, reduced thymus index and spleen index, inhibited T/B cells proliferation, alleviated the histopathology of spleen and joints in CIA mice. 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-NF-κB65. Compared with biological agents etanercept and rituximab, CP-25 restored high T cells proliferation and percentages of B subsets to normal level, and recovered the high levels of IgA, IgD, IgG1, IgG2a and high expressions molecules in NF- κB signaling to normal levels. The action intensity of rituximab and etanercept was more strong than CP- 25. The inhibitor effects of rituximab and etanercept on AI and SJC, thymus index, proliferation of T cells and B cells subsets were strong, and down-regulated the indexes to under normal levels. 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-NF-κB signaling.
