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

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• 作者：Xiaoyi Jia¹ ; Fang Wei¹ ; Xiaojing Sun¹ ; Yan Chang ; Shu Xu ; Xuezhi Yang ; Chun Wang ; Wei Wei ; ^{wwei@ahmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：RA ; rheumatoid arthritis ; FLS ; fibroblast-like synoviocytes ; BAFF ; B cell activating factor belonging to the TNF family ; TACI ; transmembrane activator and calcium modulator and cyclophilin ligand interactor ; BCMA ; B-cell maturation antigen ; BAFF-R ; BAFF receptor ; APRIL ; a proliferation-inducing ligand ; TGP ; total glucosides of paeony ; Pae ; paeoniflorin ; CP-25 ; paeoniflorin-6&prime ; -O-benzene sulfonate ; AA ; rat adjuvant-induced arthritis ; MLN ; mesenteric lymph node ; CIA ; collagen-induced arthriti
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：2 August 2016
• 年：2016
• 卷：189
• 期：Complete
• 页码：194-201
• 全文大小：1800 K

文摘

Total glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug approved for the treatment of rheumatoid arthritis in China. A novel compound, paeoniflorin-6′-O-benzene sulfonate (code CP-25), comes from the structural modification of paeoniflorin (Pae), which is the effective active ingredient of TGP. The aim of the present study is to investigate the effect of CP-25 on adjuvant arthritis (AA) fibroblast-like synoviocytes (FLS) co-cultured with BAFF-activated CD4⁺ T cells and the expression of BAFF-R in CD4⁺ T cells.

Methods

The mRNA expression of BAFF and its receptors was assessed by qPCR. The expression of BAFF receptors in CD4⁺ T cells was analyzed by flow cytometry. The effect of CP-25 on AA rats was evaluated by their joint histopathology. The cell culture growth of thymocytes and FLS was detected by cell counting kit (CCK-8). The concentrations of IL-1β, TNF-α, and IL-6 were measured by Enzyme-linked immunosorbent assay (ELISA).

Results

The mRNA expression levels of BAFF and BAFF-R were enhanced in the mesenteric lymph nodes of AA rats, TACI expression was reduced, and BCMA had no change. The expression of BAFF-R in CD4⁺ T cells was also enhanced. CP-25 alleviated the joint histopathology and decreased the expression of BAFF-R in CD4⁺ T cells from AA rats in vivo. In vitro, CP-25 inhibited the abnormal cell culture growth of BAFF-stimulated thymocytes and FLS. In the co-culture system, IL-1β, IL-6 and TNF-α production was enhanced by FLS co-cultured with BAFF-activated CD4⁺ T cells. Moreover, BAFF-stimulated CD4⁺ T cells promoted the cell culture growth of FLS. The addition of CP-25 decreased the expression of BAFF-R in CD4⁺ T cells and inhibited the cell culture growth and cytokine secretion ability of FLS co-cultured with BAFF-activated CD4⁺ T cells.

Conclusion

The present study indicates that CP-25 may repress the cell culture growth and cytokine secretion ability of FLS, 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. These observations might provide a scientific basis for the development of new drugs for the treatment of autoimmune diseases by CP-25.