CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells. (2nd August 2016)

• Record Type: Journal Article
• Authors: Jia, Xiaoyi; Wei, Fang; Sun, Xiaojing; Chang, Yan; Xu, Shu; Yang, Xuezhi; Wang, Chun; Wei, Wei
• Is Part Of: Journal of ethnopharmacology. Volume 189(2016)
• Page Start: 194
• Page End: 201
• Publication Date: 2016-08-02
• Subjects: 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′-O-benzene sulfonate -- AA rat adjuvant-induced arthritis -- MLN mesenteric lymph node -- CIA collagen-induced arthritis; Adjuvant-induced arthritis -- CD4+ -- T cells -- Fibroblast-like synoviocytes -- BAFF -- BAFF-R, Paeoniflorin-6′-O-benzene sulfonate; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2016.05.034
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: 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 syn oviocytes (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. Graphical abstract: