Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, People's Republic of China.
J Clin Immunol. 2010 Jan;30(1):24-33. doi: 10.1007/s10875-009-9329-1. Epub 2009 Sep 30.
Previous studies show that cyclophilin A (CypA) acts as a strong chemotactic cytokine to neutrophils, eosinophils, and monocytes in rheumatoid arthritis (RA).
In this study, monocytes were stimulated by purified CypA and the production of matrix metalloproteinase (MMPs), the cell invasion and the release of inflammatory cytokines were detected respectively by gelatin zymography, invasion assay, and cytometric bead array FCM.
The elevated level of inflammatory cytokine IL-8 was also detected. Results showed that CypA significantly promoted the invasion of THP-1 cells and increased the production of MMP-2 and MMP-9, which displayed a biphasic concentration dependency. In vivo experiments found that the cartilage erosion scores in CypA injection group were significantly higher than those in control group (P < 0.05).
Our findings suggest that CypA significantly enhances the secretion of MMP-2 and MMP-9, the cell invasion, and the inflammatory cytokines production of monocytes. Our findings may shed some new light on the inflammatory process and the degradation of cartilage and bone in RA.
先前的研究表明,亲环素 A(CypA)在类风湿关节炎(RA)中作为一种强大的趋化细胞因子,作用于中性粒细胞、嗜酸性粒细胞和单核细胞。
在这项研究中,通过纯化的 CypA 刺激单核细胞,分别通过明胶酶谱法、侵袭试验和流式细胞术检测细胞外基质金属蛋白酶(MMPs)的产生、细胞侵袭和炎症细胞因子的释放。
还检测到炎症细胞因子 IL-8 的水平升高。结果表明,CypA 显著促进了 THP-1 细胞的侵袭,并增加了 MMP-2 和 MMP-9 的产生,呈双相浓度依赖性。体内实验发现,CypA 注射组的软骨侵蚀评分明显高于对照组(P<0.05)。
我们的研究结果表明,CypA 显著增强了单核细胞的 MMP-2 和 MMP-9 的分泌、细胞侵袭和炎症细胞因子的产生。我们的发现可能为 RA 中的炎症过程和软骨及骨的降解提供一些新的见解。