Expression and function of 尾-arrestin 2 stimulated by IL-1尾 in human fibroblast-like synoviocytes and the effect of paeoniflorin
- 作者：Hua-Xun Wu wuhuaxun@yahoo.cn ; Jing-Yu Chen cjy.anyi@gmail.com ; Qing-Tong Wang hfwqt727@163.com ; Wu-Yi Sun ; Li-Hua Liu liulihuawomen@hotmail.com ; Ling-Ling Zhang llzhang@ahmu.edu.cn ; Wei Wei ; wwei@ahmu.edu.cn
- 关键词：RA ; rheumatoid arthritis ; AA ; adjuvant arthritis ; CIA ; collagen-induced arthritis ; FLS ; fibroblast-like synoviocytes ; GPCRs ; G-protein-coupled receptors ; Pae ; paeoniflorin ; PBMC ; peripheral blood mononuclear cells ; MLN ; mesenteric lymph nodes ; 7TMRs ; 7 tr
- 刊名：International Immunopharmacology
- 出版年：2012
- 期刊代码：123_15675769
- 类别：med
- 出版时间：April, 2012
- 卷：12
- 期：4
- 页码：701-706
- 文件大小：539 K
摘要
The aim of this study was to explore the expression and function of 尾-arrestin 2 in human fibroblast-like synoviocytes (FLS) stimulated by IL-1尾 and the effect of paeoniflorin (Pae). We isolated and cultured human FLS, which were stimulated by IL-1尾. The FLS proliferations were detected by [3H] thymidine incorporation. The level of cAMP stimulated by IL-1尾 on different times was investigated by radioimmunoassay, and the activity of PKA was measured by luminescent kinase assay. The expression of 尾-arrestin 2 was measured by western blot. We found that the human FLS proliferation increased apparently in 24 h, and the activities of PKA and cAMP accumulation increased significantly in 6 h after stimulated by IL-1尾, while cAMP accumulation and the activities of PKA decreased especially in 24 h when the expression of 尾-arrestin 2 increased significantly. Decreased cAMP accumulation and the increased expression of 尾-arrestin 2 may reveal a positive correlation with the FLS proliferation. Pae (10- 5, 10- 6, 10-7 mol鈥- 1) in vitro could suppress the FLS proliferation and the high expression of 尾-arrestin 2. The expression of 尾-arrestin 2 may have a positive correlation with the human FLS proliferation, while the activities of PKA and cAMP accumulation have a negative correlation with the proliferation. The increased 尾-arrestin 2 may down-regulate cAMP-PKA signaling pathway and promote FLS proliferation. Pae may suppress the expression of 尾-arrestin 2 and up-regulate cAMP-PKA signaling, which may be one of the mechanisms for the effects of Pae on inhibiting human FLS proliferation.