Department of Biochemistry and Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, Slovenia.
Biol Chem. 2010 May;391(5):571-9. doi: 10.1515/BC.2010.035.
Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. Their accumulation in synovial fluid of primarily rheumatoid arthritis patients is also well documented. However, a detailed comparison between the protease levels and activities between rheumatoid arthritis samples and osteoarthritis samples has never been made. Here, we report that both cysteine cathepsins B and S and matrix metalloproteases-1, -3 and -13 are detected in patient synovial fluid samples with significantly higher levels detected in rheumatoid arthritis patients. Among the proteases, cathepsin S was found to be significantly elevated, consistent with its critical role in the immune response. These results suggest that cysteine cathepsins have a major role in inflammation at least in rheumatoid arthritis. In addition to proteases, interleukin-6 was detected at significant levels in most samples, suggesting that proinflammatory cytokines might be in-volved in the stimulation of expression of these proteases during inflammation.
半胱氨酸组织蛋白酶和基质金属蛋白酶被认为在关节炎疾病的发展中发挥重要作用。它们在主要是类风湿关节炎患者的滑液中的积累也有充分的记录。然而,类风湿关节炎样本和骨关节炎样本之间的蛋白酶水平和活性的详细比较从未进行过。在这里,我们报告说,半胱氨酸组织蛋白酶 B 和 S 以及基质金属蛋白酶-1、-3 和-13 都在患者的滑液样本中被检测到,在类风湿关节炎患者中检测到的水平明显更高。在这些蛋白酶中,发现组织蛋白酶 S 显著升高,与其在免疫反应中的关键作用一致。这些结果表明,半胱氨酸组织蛋白酶在炎症中至少在类风湿关节炎中发挥主要作用。除了蛋白酶外,白细胞介素-6 在大多数样本中也被检测到显著水平,这表明促炎细胞因子可能参与了这些蛋白酶在炎症过程中的表达刺激。