CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells

Jia, Xiaoyi; Fang, Wei; Sun, Xiaojing; Cao, Yan; Xu, Shu; Yang, Xiaofang; Wang, Chun; Wei, Wei

doi:10.1016/j.jep.2016.05.034

Cited by 30 publications

(20 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In CIA mice and an AA rat model, the BAFF levels were significantly high [30,38]. The study by Jia et al showed that the mRNA expressions of BAFF and BAFFR were increased in the mesenteric lymph nodes in AA rats [43]. In the research by Tue G et al, BAFF exerted a positive effect on the maturation and proliferation of B cells [44].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents

et al. 2018

Self Cite

View full text Add to dashboard Cite

Paeoniflorin-6′-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19 + total B cells, CD19 + CD27 +-activated B cells, CD19 + BAFFR + and CD19 + TACI + cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19 + TRAF2 + cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger antiinflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.

show abstract

Section: Discussionmentioning

confidence: 99%

“…BAFF is one of the major factors regulating B-cell development and homeostasis through the binding of its three receptors [43]. In CIA mice and an AA rat model, the BAFF levels were significantly high [30,38].…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The protective effects of this compound during adjuvant-induced arthritis have been reported recently ( Chang et al, 2016 ). In vitro studies have illustrated that CP-25 inhibits the growth and cytokine secretion ability of FLSs in a rat model of RA ( Jia et al, 2016 ). Its therapeutic effect was related to the regulation of T/B cells and FLSs.…”

Section: Discussionmentioning

confidence: 99%

“…We also found that CP-25 could regulate dendritic cell (DC) function and inhibit DC maturation in vitro ( Li et al, 2015 ). It can also attenuate the inflammatory response of BAFF-activated CD4 + T cells ( Jia et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human

Chen

et al. 2018

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4+ T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4+ T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4+ T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr394). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4+ T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr394) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4+ T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

show abstract

“…Figure 1 shows the chemical construction of CP-25. The previous studies in our laboratory demonstrated that CP-25 significantly inhibited the progression of adjuvant arthritis rats by reducing inflammation, immunity, and bone damage primarily by modulating inflammatory mediators and immune responses, particularly Th17-IL-17 and CP-25 might repress the cell culture growth and cytokine secretion ability of fibroblast synovial cells (FLSs), and its inhibitory effects might be associated with its ability to inhibit the expression of BAFF-R in CD4 + T cells in a co-culture ( Chang et al, 2016 ; Jia et al, 2016 ). At the same time, our team also found that CP-25 could inhibit the maturation of dendritic cells stimulated by TNF-alpha or Prostaglandin E2 (PGE2) through down-regulating the expression of MHC-II, CD40, CD80, CD83, and CD86 ( Li et al, 2015 ), which suggested that CP-25 could regulate the function of immune cells.…”

Section: Introductionmentioning

confidence: 99%

CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

et al. 2017

Self Cite

View full text Add to dashboard Cite

Paeoniflorin-6′-O-benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

show abstract

CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells

Cited by 30 publications

References 52 publications

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents

CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human

CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

Contact Info

Product

Resources

About