title: Expression and function of β-arrestin 2 stimulated by IL-1β in human fibroblast-like synoviocytes and the effect of paeoniflorin.
abstract: The aim of this study was to explore the expression and function of β-arrestin 2 in human fibroblast-like synoviocytes (FLS) stimulated by IL-1β and the effect of paeoniflorin (Pae). We isolated and cultured human FLS, which were stimulated by IL-1β. The FLS proliferations were detected by [3H] thymidine incorporation. The level of cAMP stimulated by IL-1β on different times was investigated by radioimmunoassay, and the activity of PKA was measured by luminescent kinase assay. The expression of β-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-1β, while cAMP accumulation and the activities of PKA decreased especially in 24 h when the expression of β-arrestin 2 increased significantly. Decreased cAMP accumulation and the increased expression of β-arrestin 2 may reveal a positive correlation with the FLS proliferation. Pae (10(-5), 10(-6), 10-7 mol•L(-1)) in vitro could suppress the FLS proliferation and the high expression of β-arrestin 2. The expression of β-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 β-arrestin 2 may down-regulate cAMP-PKA signaling pathway and promote FLS proliferation. Pae may suppress the expression of β-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.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China Key Laboratory of Antiinflammatory and Immunopharmacology, Ministry of Education, China, Hefei, 230032, China. wuhuaxun@yahoo.cn
authors.forename: Hua-Xun
authors.initials: HX
authors.lastname: Wu
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.forename: Wu-Yi
authors.initials: WY
authors.lastname: Sun
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Liu
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D039821:Monoterpenes; D029596:Paeonia; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D006027:Glycosides
chemical_list: D019390:Arrestins; D001565:Benzoates; D001952:Bridged-Ring Compounds; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005960:Glucosides; D053583:Interleukin-1beta; D039821:Monoterpenes; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C000605254:ARRB2 protein, human; C015423:peoniflorin; D006027:Glycosides