EXPRESSION OF HUMAN TENASCIN IN SYNOVITIS AND ITS REGULATION BY INTERLEUKIN-1

Objective. Tenascin is an extracellular matrix glycoprotein with effects on cell adhesion, cell migration, and lymphocyte activation. We proposed to identify the expression of human tenascin messenger RNA (mRNA) and protein in inflammatory synovitis and in normal synovium, and to identify potential regulatory cytokines. Methods. Immunohistochemistry and in situ hybridization were used to identify the expression of tenascin in synovium. Northern blot analysis of RNA and both immunoblot analysis and enzyme-linked immunosorbent assay of proteins were used to identify tenascin in synovial cell cultures. Results. Tenascin was found along the synovial lining layer and in perivascular areas of normal synovium. In inflammatory synovitis, tenascin protein and mRNA expression were shown to be increased in the synovial lining layer, in perivascular areas, in lymphoid aggregates, and in areas of fibrosis. Interleukin-1, a major mediator of tissue injury in inflammatory synovitis, induced tenascin expression and deposition in primary synovial fibroblast cultures. Conclusion. Tenascin mRNA and protein are increased in inflammatory synovitis, and interleukin-1 is an inducer of tenascin in synovial fibroblasts. This identifies a new pathway by which interleukin-1 alters the extracellular matrix composition in synovitis. Since tenascin has effects on lymphocyte activation and cell adhesion, the induction of tenascin in inflammatory synovitis may play a role in the pathophysiology of arthritis.