TSG-6 EXPRESSION IN HUMAN ARTICULAR CHONDROCYTES - POSSIBLE IMPLICATIONS IN JOINT INFLAMMATION AND CARTILAGE DEGRADATION

Objective. The hyaluronan-binding protein TSG-6 (tumor necrosis factor -stimulated gene 6) forms a stable complex with the serine protease in hibitor, inter-alpha-inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examine s the expression of TSG-6 in human articular chondrocytes and cartilag e. Methods. Human articular chondrocytes and cartilage explants were s timulated with cytokines, growth factors, and other agents, TSG-6 expr ession was analyzed by imaging-assisted Northern and Western blotting. Results. TSG-6 messenger RNA (mRNA) expression was upregulated by cyt okines and growth factors, predominantly interleukin-1 beta (IL-1 beta ), tumor necrosis factor alpha (TNF alpha), platelet-derived growth fa ctor 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-1 beta. Treatment of the cells with the glucocorticoid dexamethasone nei ther 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 contras t, PKA- and Ca-dependent signals are only marginally involved as messe ngers leading to increased TSG-6 levels after IL-1 beta 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 pre sent and upregulated by IL-1 beta, TNF alpha, or TGF beta 1. Conclusio n. Chondrocytes are a source of TSG-6 which may play a role in cartila ge remodeling and joint inflammation.