Transforming growth factor beta 1 and interleukin 4 induced alpha smooth muscle actin expression and myofibroblast-like differentiation in human synovial fibroblasts in vitro: modulation by basic fibroblast growth factor
Transforming growth factor beta 1 and interleukin 4 induced alpha smooth muscle actin expression and myofibroblast-like differentiation in human synovial fibroblasts in vitro: modulation by basic fibroblast growth factor
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DOI：
10.1136/ard.56.7.426
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发表时间：
1997-07-01
影响因子：
27.4
通讯作者：
Slater, H
中科院分区：
文献类型：
--
作者：
Mattey, DL;Dawes, PT;Slater, H
目的 - 探究类风湿关节炎（RA）发炎关节中存在的细胞因子是否会诱导滑膜成纤维细胞中平滑肌肌动蛋白表达以及肌成纤维细胞分化。
方法 - 采用免疫荧光显微镜和蛋白质印迹法，在细胞因子转化生长因子β（TGFβ1）、白细胞介素1α（IL1α）、IL4、IL6、肿瘤坏死因子α（TNFα）和碱性成纤维细胞生长因子（FGF）存在的情况下，检测不同培养条件下的人类滑膜成纤维细胞中α肌动蛋白的表达。
结果 - 在标准培养条件下，有一小部分但数量显著的细胞（14.4 ± 12.9%）表达α肌动蛋白。经TGFβ1处理后，表达α肌动蛋白的细胞数量显著增加（68.1 ± 5.49%），同时细胞形态转变为肌成纤维细胞样表型。在发炎关节中发现的其他细胞因子，如IL1、TNFα、IL6和碱性FGF，未能诱导α肌动蛋白表达。然而，在RA关节中通常不存在或仅以低浓度存在的IL4，具有与TGFβ1相似的作用。还发现碱性FGF抑制TGFβ1和IL4对α肌动蛋白表达的诱导作用。
结论 - 在TGFβ1或IL4存在的情况下，源自滑膜组织或滑膜液的成纤维细胞被诱导分化为含有α平滑肌形式肌动蛋白的肌成纤维细胞样细胞。这种分化被碱性FGF抑制。提示这些特定细胞因子之间的平衡可能在调节成纤维细胞行为方面具有重要作用，这可能对类风湿关节内的关节修复机制和纤维组织的生成产生重大影响。
Objective-To discover if a smooth muscle actin expression and myofibroblastic differentiation are induced in synovial fibroblasts by cytokines found in the inflamed RA joint.Methods-Immunofluorescent microscopy and western blotting were used to examine different cultures of human synovial fibroblasts for expression of a actin in the presence of the cytokines transforming growth factor beta (TGF beta 1), interleukin 1 alpha (IL1 alpha), IL4, IL6, tumour necrosis factor alpha (TNF alpha), and basic fibroblast growth factor (FGF).Results-A small but significant population of cells (14.4 +/- 12.9%) expressed alpha actin under standard culture conditions. Upon treatment with TGF beta 1 there was a pronounced increase in the number of cells expressing alpha actin (68.1 +/- 5.49%), accompanied by a change in morphology to a myofibroblast-like phenotype. Other cytokines found within the inflamed joint such as IL1, TNF alpha, IL6, and basic FGF failed to induce alpha actin expression. However, IL4, which is normally absent or only present at low concentrations in the RA joint had a similar effect to TGF beta 1. It was also found that basic FGF inhibited the induction of alpha actin expression by TGF beta 1 and IL4.Conclusion-In the presence of TGF beta 1 or IL4, fibroblasts derived from synovial tissue or synovial fluid are induced to differentiate into myofibroblast-like cells containing the alpha smooth muscle form of actin. This differentiation is inhibited by basic FGF. It is suggested that the balance between these particular cytokines may be important in the modulation of fibroblast behaviour, which could have significant effects on joint repair mechanisms and the generation of fibrous tissue within the rheumatoid joint.