Shanghai Ocean University, No. 999, Hu Cheng Loop-road, Lingang New City, Shanghai 201306, China.
Pharmaceuticals (Basel). 2012 Mar 28;5(4):339-52. doi: 10.3390/ph5040339.
Shark type II collagen (SCII) is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca). We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund's Adjuvant (CFA).
The onset of rheumatoid arthritis (RA) was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg-1d-1, days 14-28), while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg-1d-1, days 14-28), Tripterygium wilfordii polyglycosidium (TWP) (10 mg kg-1d-1, days 14-28), and bovine type II collagen from US (US-CII) (1 mg kg-1d-1, days 14-28), respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH) reaction, the level of interleukins 10 (IL-10) in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC) was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII.
Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg-1d-1 (SCII 3) and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced.
Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral administration of SCII might be a potential candidate as a novel drug for further investigation.
从蓝鲨(Prionace glauca)软骨中提取鲨鱼 II 型胶原蛋白(SCII),作为糖蛋白。我们旨在证实口服鲨软骨 II 型胶原蛋白(SCII)对完全弗氏佐剂(CFA)诱导的类风湿关节炎大鼠踝关节炎症和免疫反应的口服耐受作用。
在注射 CFA 后 14±x 天观察到类风湿关节炎(RA)的发病。对照组大鼠用醋酸经口给药(0.05mmol/kg-1d-1,第 14-28 天),实验组大鼠分别用 SCII(1 或 3mg/kg-1d-1,第 14-28 天)、雷公藤多苷(TWP)(10mg/kg-1d-1,第 14-28 天)和美国牛 II 型胶原蛋白(US-CII)(1mg/kg-1d-1,第 14-28 天)经口给药。通过关节肿胀评估关节炎的严重程度。观察的免疫学指标包括迟发型超敏反应(DTH)反应、大鼠血清白细胞介素 10(IL-10)水平和形态学特征。进行混合淋巴细胞培养(MLC),以研究 SCII 诱导的 T 细胞凋亡与特异性免疫耐受之间的关系。
连续 2 周用 SCII 治疗可显著减轻急性炎症。与对照组相比,口服 SCII 3mg/kg-1d-1(SCII 3)和 US-CII 的大鼠 DTH 反应降低。SCII 3 组大鼠的 IL-10 水平最高,为 102pg/ml。浓度为 10μg/L 的 SCII 可显著提高体外 T 细胞中 Fas/Apo-1 的水平。组织学染色结果表明,SCII 3 组踝关节关节膜的恢复明显增强。
我们的结果表明,适当剂量的 SCII 不仅可以改善症状,而且可以改变完全弗氏佐剂诱导的关节炎的疾病过程。口服 SCII 可能是一种有前途的新型药物候选物,值得进一步研究。