A novel anti-inflammatory and immunomodulatory drug CP-25 alleviated collagen induced arthritis by d

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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,IgG2 a 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. 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- 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- 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, C. D19 + 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- KB65.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, IgG2 a 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-κΒ signaling.
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