代谢激活刺激滑膜成纤维细胞产酸。

Metabolic activation stimulates acid production in synovial fibroblasts.

作者信息

Parak W J, Dannöhl S, George M, Schuler M K, Schaumburger J, Gaub H E, Müller O, Aicher W K

机构信息

Institute of Applied Physics, University of Munich, Germany.

出版信息

J Rheumatol. 2000 Oct;27(10):2312-22.

PMID:11036823

Abstract

OBJECTIVE

In rheumatoid arthritis (RA), synovial fibroblasts express proteases such as collagenases or cathepsins and inflammatory cytokines at elevated levels and so contribute to the inflammatory degradation process. Extracellular matrix degradation and cathepsin activity is dependent upon the presence of an acidic milieu. We examined whether activated synovial fibroblasts secrete acidic components.

METHODS

Synovial fibroblasts were isolated and immortalized to study the mechanisms of metabolic activation. Naïve and immortalized fibroblasts were activated with different cytokines. The responses were investigated by immunoblot to detect Egr-1 and by a cytosensor microphysiometer analysis to evaluate acid secretion. Basic gene expression patterns were investigated in naïve and immortalized cells by RT-PCR analysis.

RESULTS

We found RA synovial fibroblasts respond to different cytokines associated with the pathomechanisms of RA including interleukin 1, basic fibroblast growth factor, platelet derived growth factor, and tumor necrosis factor-alpha, with metabolic activation and enhanced secretion of acidic components. In addition, naive and SV40 TAg immortalized fibroblasts rapidly release acidic components after stimulation with phorbol ester or ionomycin as well.

CONCLUSION

Activated synovial fibroblasts not only express inflammatory cytokines and matrix degrading proteases that are associated with the pathomechanisms of RA, but upon stimulation may release acidic components that lower pH and consequently enhance cathepsin activity and collagen solubilization.

摘要

目的

在类风湿关节炎（RA）中，滑膜成纤维细胞高水平表达诸如胶原酶或组织蛋白酶等蛋白酶以及炎性细胞因子，从而促进炎症性降解过程。细胞外基质降解和组织蛋白酶活性依赖于酸性环境的存在。我们研究了活化的滑膜成纤维细胞是否分泌酸性成分。

方法

分离滑膜成纤维细胞并使其永生化以研究代谢活化机制。用不同的细胞因子激活未活化的和永生化的成纤维细胞。通过免疫印迹检测早期生长反应蛋白-1（Egr-1）以及通过细胞传感器微生理仪分析评估酸分泌来研究反应情况。通过逆转录-聚合酶链反应（RT-PCR）分析研究未活化的和永生化细胞中的基本基因表达模式。

结果

我们发现RA滑膜成纤维细胞对与RA发病机制相关的不同细胞因子（包括白细胞介素1、碱性成纤维细胞生长因子、血小板衍生生长因子和肿瘤坏死因子-α）产生反应，出现代谢活化并增强酸性成分的分泌。此外，未活化的和成猿猴病毒40大T抗原（SV40 TAg）永生化的成纤维细胞在用佛波酯或离子霉素刺激后也会迅速释放酸性成分。