韩国科学家最近通过研究发现一种被称为‘calcineurin’的细胞内的信号蛋白质是导致 rheumatoid关节炎发病的一个主要原因。这在学术界尚属首次。
rheumatoid关节炎是一种非常典型的免疫疾病，它具有关节组织和溃疡一起生长，从而导致不正常现象出现的特征。在这一过程中一种被称为‘calcineurin’的蛋白质会导致免疫系统地异常，从而导致rheumatoid关节炎的产生。而calcineurin正是引起rheumatoid关节炎的核心物质。
科学技术部(副总理兼长官金雨植)和韩国科学财团(理事长权五甲)共同出资的System Bio Dynamics研究中心金完郁教授研究小组与圣母医院的赵哲洙教授共同合作，得出了这一结论。
这一研究结果于2006年8月被发表在免疫学领域的权威刊物美国免疫学学会杂志(Journal of Immunology)上，成为这一月最受大家瞩目的话题。
Calcineurin的增加与人体内钙质的增加有着非常密切的关系，而发现rheumatoid关节炎等慢性疾病与钙质(calcium)的非正常现象有关这在学术界尚属首次。
在发现这一发病原因的同时，研究小组还通过对动物(活老鼠)的试验，通过抑制calcineurin的方法来矫正关节细胞的非正常现象，从而减少关节炎的发病现象。
特别是金教授的研究小组发现在使用自然的calcineurin抑制蛋白质(Cabin)基因来治疗关节炎时，不仅没有副作用还可以强力抑制关节炎的发病，并就此提出了新的假设。
这一研究结果将可以应用于治疗包括rheumatoid关节炎在内的慢性炎症性肠疾病、1型糖尿病、免疫性肺炎、葡萄膜炎、脏器移植抗拒反应等多种多样的免疫疫病。
英文原文：
Calcineurin Is Expressed and Plays a Critical Role in Inflammatory Arthritis
Calcineurin is a calcium-activated phosphatase to mediate lymphocyte activation and neuron signaling, but its role in inflammatory arthritis remains largely unknown. In this study, we demonstrate that calcineurin was highly expressed in the lining layer, infiltrating leukocytes, and endothelial cells of rheumatoid synovium. The basal expression levels of calcineurin were higher in the cultured synoviocytes of rheumatoid arthritis patients than those of osteoarthritis patients. The calcineurin activity in the synoviocytes was increased by the stimulation with proinflammatory cytokines such as IL-1 and TNF-. Moreover, rheumatoid arthritis synoviocytes had an enlarged intracellular Ca2+ store and showed a higher degree of [Ca2+]i release for calcineurin activity than osteoarthritis synoviocytes when stimulated with either TNF- or phorbol myristate acetate. IL-10, an anti-inflammatory cytokine, failed to increase the Ca2+ and calcineurin activity. The targeted inhibition of calcineurin by the overexpression of calcineurin-binding protein 1, a natural calcineurin antagonist, inhibited the production of IL-6 and matrix metalloproteinase-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. Moreover, the abundant calcineurin expression was found in the invading pannus in the joints of mice with collagen-induced arthritis. In these mice, calcineurin activity in the cultured synovial and lymph node cells correlated well with the severity of arthritis, but which was suppressed by cyclosporin A treatment. Taken together, our data suggest that the abnormal activation of Ca2+ and calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis and thus provide a potential target for controlling inflammatory arthritis.
