肿瘤坏死因子-α（TNF-α）转换酶有助于类风湿关节炎患者滑膜组织中TNF-α的产生。
Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF-alpha in synovial tissues from patients with rheumatoid arthritis.
作者信息
Ohta S, Harigai M, Tanaka M, Kawaguchi Y, Sugiura T, Takagi K, Fukasawa C, Hara M, Kamatani N
机构信息
Institute of Rheumatology, Tokyo Women's Medical University, Japan.
出版信息
J Rheumatol. 2001 Aug;28(8):1756-63.
OBJECTIVE
Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA.
METHODS
Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate.
RESULTS
Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells.
CONCLUSION
TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.
目的
检测类风湿关节炎（RA）患者滑膜中肿瘤坏死因子-α（TNF-α）转换酶（TACE）的表达及功能，以研究RA中TACE对TNF-α产生的翻译后调控。
方法
采用免疫组织化学法评估TACE蛋白的表达。通过酶联免疫吸附测定（ELISA）检测细胞因子和可溶性细胞因子受体。用逆转录聚合酶链反应（RT-PCR）检测TACE mRNA。使用TACE特异性荧光底物测量TACE的酶活性。
结果
RA患者滑膜组织（ST）中TACE蛋白水平的表达明显强于骨关节炎（OA）患者。在RA中，TACE主要表达于CD68 +巨噬样滑膜细胞。9例RA患者中的9例以及8例OA患者中的3例的ST表达TACE mRNA。RA ST细胞具有比OA ST明显更高的TACE样酶活性。一种合成的TACE抑制剂显著降低了RA ST细胞中TNF-α和p75 TNF受体的释放。
结论
TACE是RA患者滑膜中TNF-α分泌的重要调节因子。
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