Maier R, Wisniewski H G, Vilcek J, Lotz M
University of California, San Diego, La Jolla 92093-0663, USA.
Arthritis Rheum. 1996 Apr;39(4):552-9. doi: 10.1002/art.1780390403.
The hyaluronan-binding protein TSG-6 (tumor necrosis factor-stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter-alpha-inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG-6 in human articular chondrocytes and cartilage.
Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG-6 expression was analyzed by imaging-assisted Northern and Western blotting.
TSG-6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), platelet-derived growth factor AA (PDGF-AA), and transforming growth factor beta 1 (TGF beta 1). TSG-6 mRNA induction by TGF beta 1 was delayed as compared with IL-1beta. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG-6 mRNA nor did it affect IL-1 beta-induced transcript levels. TSG-6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)-mediated signaling. In contrast, PKA- and Ca- dependent signals are only marginally involved as messengers leading to increased TSG-6 levels after IL-1beta and TNF alpha treatment. In chondrocyte and cartilage organ cultures, both free TSG-6 (35 kd) and the complex with inter-alpha-inhibitor (120 kd) were present and upregulated by IL-1 beta, TNF alpha, or TGF beta 1.
Chondrocytes are a source of TSG-6 which may play a role in cartilage remodeling and joint inflammation.
透明质酸结合蛋白TSG-6（肿瘤坏死因子刺激基因6）与丝氨酸蛋白酶抑制剂（α-抑制因子）形成稳定复合物，增强对纤溶酶活性的抑制作用，并在体内具有抗炎作用。本研究检测TSG-6在人关节软骨细胞和软骨中的表达。
用人细胞因子、生长因子和其他试剂刺激人关节软骨细胞和软骨外植体。通过成像辅助Northern印迹和Western印迹分析TSG-6的表达。
细胞因子和生长因子可上调TSG-6信使核糖核酸（mRNA）的表达，主要包括白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNFα）、血小板衍生生长因子AA（PDGF-AA）和转化生长因子β1（TGFβ1）。与IL-1β相比，TGFβ1诱导TSG-6 mRNA的时间延迟。用糖皮质激素地塞米松处理细胞既不诱导TSG-6 mRNA表达，也不影响IL-1β诱导的转录水平。TSG-6 mRNA的诱导可能涉及多种信号转导途径。佛波酯肉豆蔻酸酯强烈的转录刺激表明蛋白激酶C（PKC）介导的信号传导。相比之下，蛋白激酶A（PKA）和钙依赖性信号仅在较小程度上作为信使参与IL-1β和TNFα处理后导致TSG-6水平升高的过程。在软骨细胞和软骨器官培养物中，游离TSG-6（35 kDa）和与α-抑制因子的复合物（120 kDa）均存在，并被IL-1β、TNFα或TGFβ1上调。
软骨细胞是TSG-6的来源，TSG-6可能在软骨重塑和关节炎症中发挥作用。
