期刊
JOURNAL OF ETHNOPHARMACOLOGY
卷 189, 期 -, 页码 194-201出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2016.05.034
关键词
Adjuvant-induced arthritis; CD4(+); T cells; Fibroblast-like synoviocytes; BAFF; BAFF-R, Paeoniflorin-6'-O-benzene sulfonate
资金
- National Natural Science Foundation of China [31200675, 81173075, 81330081, 81302845]
- Specialized Research Fund for the Doctoral Program of Higher Education [20123420110003]
- Grants for Scientific Research of BSKY from Anhui Medical University [XJ201215]
Ethnopharinacological 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 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-1 beta, TNF-alpha, 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 BAFFR 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-1 beta, IL-6 and TNF-alpha 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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