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

Jin-ling SHU,Xian-zheng ZHANG,Le HAN,Feng ZHANG,Yu-jing WU,Xiao-yu Tang,Chen WANG,Yu TAI,Qing-tong WANG,Jing-yu CHEN,Ling-ling ZHANG,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Hefei 230032,China)

T1-26

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

Jin-ling SHU,Xian-zheng ZHANG,Le HAN,Feng ZHANG,Yu-jing WU,Xiao-yu Tang,Chen WANG,Yu TAI,Qing-tong WANG,Jing-yu CHEN,Ling-ling ZHANG,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Hefei 230032,China)

OBJECTIVETo 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.METHODSMice 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.RESULTSCP-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.CONCLUSIONCP-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.

collagen induced-arthritis;B cell;BAFF;CP-25;comparison efficacy;biological agents

The project supported by National Natural Science Foundation of China(81330081,81473223 and 81673444);and Anhui Province Postdoctoral Science Foundation(2016B134)

Ling-ling ZHANG,Tel:13856001266,E-mail：llzhang@ahmu.edu.cn;Wei WEI,Tel:13605510563,E-mail：wwei@ahmu.edu.cn