聚脱氧核糖核苷酸通过刺激腺苷A₂A受体减少细胞因子产生及胶原诱导性关节炎的严重程度。

Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(₂A) receptor.

作者信息

Bitto Alessandra, Polito Francesca, Irrera Natasha, D'Ascola Angela, Avenoso Angela, Nastasi Giancarlo, Campo Giuseppe M, Micali Antonio, Bagnato Gianfilippo, Minutoli Letteria, Marini Herbert, Rinaldi Mariagrazia, Squadrito Francesco, Altavilla Domenica

机构信息

University of Messina, Messina, Italy.

出版信息

Arthritis Rheum. 2011 Nov;63(11):3364-71. doi: 10.1002/art.30538.

DOI:10.1002/art.30538

PMID:21769841

Abstract

OBJECTIVE

Broad antiinflammatory effects following adenosine A(₂A) receptor stimulation have been demonstrated in acute inflammatory diseases, including arthritis. Polydeoxyribonucleotide (PDRN) activates the adenosine A(₂A) receptor. This study was undertaken to investigate the effects of PDRN in collagen-induced arthritis (CIA) in mice.

METHODS

Arthritis was induced in DBA/1 mice by an intradermal injection of 100 μl of bovine type II collagen in Freund's complete adjuvant. Mice were immunized a second time 21 days later. Control animals received 100 μl of a saline solution. Animals with CIA were randomized to receive one of the following: vehicle (1 ml/kg); PDRN (8 mg/kg intraperitoneally daily); 3,7-dimethyl-propargylxanthine (DMPX), a specific adenosine A(₂A) receptor antagonist (0.1 mg/kg intraperitoneally daily); or PDRN plus DMPX. The treatment was initiated immediately after the second immunization and continued to day 45. Clinical evaluation of arthritis was performed throughout the study. On day 45, the animals were killed and the severity of arthritis was evaluated histologically. Cartilage expression and circulating levels of high mobility group box chromosomal protein 1 (HMGB-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-10 were investigated. Inflammatory cytokine production was also evaluated in stimulated human chondrocytes treated with PDRN.

RESULTS

PDRN treatment significantly ameliorated clinical signs of arthritis, improved histologic damage, reduced the cartilage expression and circulating levels of HMGB-1, TNFα, and IL-6, and enhanced IL-10 expression. The concomitant administration of DMPX and PDRN ablated the PDRN-induced protective effect in experimental arthritis. PDRN also reduced cytokine production from stimulated human chondrocytes.

CONCLUSION

Our findings indicate that PDRN may represent a new alternative for the treatment of arthritis.

摘要

目的

腺苷A₂A受体激动后在包括关节炎在内的急性炎症性疾病中已显示出广泛的抗炎作用。聚脱氧核糖核苷酸（PDRN）可激活腺苷A₂A受体。本研究旨在探讨PDRN对小鼠胶原诱导性关节炎（CIA）的影响。

方法

通过在弗氏完全佐剂中皮内注射100μl牛II型胶原诱导DBA/1小鼠患关节炎。21天后对小鼠进行第二次免疫。对照动物注射100μl盐溶液。患有CIA的动物被随机分为接受以下之一：赋形剂（1ml/kg）；PDRN（每天腹腔注射8mg/kg）；3,7 - 二甲基 - 炔丙基黄嘌呤（DMPX），一种特异性腺苷A₂A受体拮抗剂（每天腹腔注射0.1mg/kg）；或PDRN加DMPX。第二次免疫后立即开始治疗并持续至第45天。在整个研究过程中对关节炎进行临床评估。在第45天，处死动物并通过组织学评估关节炎的严重程度。研究了高迁移率族蛋白盒染色体蛋白1（HMGB - 1）、肿瘤坏死因子α（TNFα）、白细胞介素 - 6（IL - 6）和IL - 10在软骨中的表达及循环水平。还用PDRN处理刺激的人软骨细胞评估炎症细胞因子的产生。