TSG-6 Background Information The TSG6 gene is transcribed in normal fibroblasts and activated by binding of the cytokines TNFå and IL-1 at AP-1 and NF-IL6 sites in its promoter. TSG-6 is a glycoprotein and a member of the hyaluronan-binding protein family, which includes cartilage link protein, proteoglycan core protein and the adhesion receptor CD44. TSG-6 is highly homologous to CD44, particularly in the hyaluronic acid-binding domain. TSG-6 is found in TNF-treated cells; its expression is rapidly activated by TNFå, IL-1 and lipopolysaccharide in normal fibroblasts, peripheral blood mononuclear cells, synovial cells and chondrocytes. The presence of TSG-6 in synovial fluid suggests a possible role in rheumatoid arthritis. TSG-6 forms a stable complex with components of the serine protease inhibitor, inter-å-inhibitor (IåI)). TSG-6 potentiates the inhibitory effect of lål on the protease activity of plasmin. Through their cooperative inhibitory effect on plasmin, TSG-6 and lål can modulate the protease network and thus inhibit inflammation.
