韓國科學(xué)家最近通過研究發(fā)現(xiàn)一種被稱為‘calcineurin’的細(xì)胞內(nèi)的信號蛋白質(zhì)是導(dǎo)致 rheumatoid關(guān)節(jié)炎發(fā)病的一個(gè)主要原因。這在學(xué)術(shù)界尚屬首次,。
rheumatoid關(guān)節(jié)炎是一種非常典型的免疫疾病，它具有關(guān)節(jié)組織和潰瘍一起生長,，從而導(dǎo)致不正常現(xiàn)象出現(xiàn)的特征,。在這一過程中一種被稱為‘calcineurin’的蛋白質(zhì)會導(dǎo)致免疫系統(tǒng)地異常,，從而導(dǎo)致rheumatoid關(guān)節(jié)炎的產(chǎn)生。而calcineurin正是引起rheumatoid關(guān)節(jié)炎的核心物質(zhì),。
科學(xué)技術(shù)部(副總理兼長官金雨植)和韓國科學(xué)財(cái)團(tuán)(理事長權(quán)五甲)共同出資的System Bio Dynamics研究中心金完郁教授研究小組與圣母醫(yī)院的趙哲洙教授共同合作,，得出了這一結(jié)論。
這一研究結(jié)果于2006年8月被發(fā)表在免疫學(xué)領(lǐng)域的權(quán)威刊物美國免疫學(xué)學(xué)會雜志(Journal of Immunology)上,，成為這一月最受大家矚目的話題,。
Calcineurin的增加與人體內(nèi)鈣質(zhì)的增加有著非常密切的關(guān)系，而發(fā)現(xiàn)rheumatoid關(guān)節(jié)炎等慢性疾病與鈣質(zhì)(calcium)的非正?，F(xiàn)象有關(guān)這在學(xué)術(shù)界尚屬首次。
在發(fā)現(xiàn)這一發(fā)病原因的同時(shí),，研究小組還通過對動物(活老鼠)的試驗(yàn),，通過抑制calcineurin的方法來矯正關(guān)節(jié)細(xì)胞的非正常現(xiàn)象,，從而減少關(guān)節(jié)炎的發(fā)病現(xiàn)象,。
特別是金教授的研究小組發(fā)現(xiàn)在使用自然的calcineurin抑制蛋白質(zhì)(Cabin)基因來治療關(guān)節(jié)炎時(shí)，不僅沒有副作用還可以強(qiáng)力抑制關(guān)節(jié)炎的發(fā)病,，并就此提出了新的假設(shè),。
這一研究結(jié)果將可以應(yīng)用于治療包括rheumatoid關(guān)節(jié)炎在內(nèi)的慢性炎癥性腸疾病、1型糖尿病,、免疫性肺炎,、葡萄膜炎、臟器移植抗拒反應(yīng)等多種多樣的免疫疫病。
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.
