title: Paeoniflorin down-regulates ATP-induced inflammatory cytokine production and P2X7R expression on peripheral blood mononuclear cells from patients with primary Sjögren's syndrome.
abstract: This study determined the effects of paeoniflorin (PF) on the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) expressed on peripheral blood mononuclear cells (PBMCs) and production of ATP-induced pro-inflammatory cytokines released by PBMCs in patients with primary Sjögren's syndrome (pSS). The pharmacological functions and cytotoxic effects of PF were dose dependent in PBMCs from 20 newly diagnosed pSS patients and 20 normal individuals. The optimum dose of PF was 100μM. PF significantly down-regulated the production of interleukin (IL)-1β and IL-6 from pSS PBMCs, and significantly inhibited ATP-induced expression of P2X7R, that might contribute to reduced IL-1β and IL-6. mRNA and protein levels of P2X7R on pSS PBMCs were significantly higher than in normal individuals (p=0.03, p<0.001). When PBMCs from subjects were stimulated in vitro with ATP in the presence of PF, P2X7R mRNA and protein levels were decreased significantly (p<0.001, p<0.001, respectively versus ATP group) in the pSS. Supernatant IL-1β and IL-6 levels were significantly lower in the PF group compared with ATP group (p<0.001, p<0.001). We show for the first time that PF-mediated reduction of IL-1β and IL-6 was due in part to the reduced expression and activation of the ATP sensor P2X7R on pSS PBMCs, indicating that PF might be useful for the management of pSS via down-regulating P2X7R expression. Thus, PF may provide a new therapeutic approach to regulate P2X7R-mediated pathologic responses of pSS.
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China. Electronic address: nbdeyycy@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Mingcai
authors.initials: M
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China.
authors.forename: Qiongyao
authors.initials: Q
authors.lastname: Gong
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Ningbo no. 2 Hospital, Ningbo, China.
authors.forename: Xiudi
authors.initials: X
authors.lastname: Wu
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D039821:Monoterpenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D006027:Glycosides
chemical_list: D000255:Adenosine Triphosphate; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D039821:Monoterpenes; D012333:RNA, Messenger; D058486:Receptors, Purinergic P2X7; C508585:IL1B protein, human; C508600:IL6 protein, human; C546468:P2RX7 protein, human; C015423:peoniflorin; D006027:Glycosides
keywords: IL-1β; IL-6; P2X7 receptor; Paeoniflorin; Primary Sjögren's syndrome