DYNAMIC EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETAS (TGF-BETA) ANDTHEIR TYPE-I AND TYPE-II RECEPTORS IN THE SYNOVIAL TISSUE OF ARTHRITIC RATS

A well characterized animal model that shares many characteristic feat ures with rheumatoid arthritis (RA) is collagen-induced arthritis (CIA ) in DA rats. Recent studies have demonstrated that TGF-beta, a multif unctional cytokine, is an important modulator of the immune response i n CIA, and possibly also in RA. In this study we have investigated the expression of the precursor forms of TGF-beta 1, TGF-beta 2, TGF-beta 3, as well as TGF-beta type I receptor (TGF-beta RI) and TGF-beta typ e II receptor (TGF-beta RII) in the synovial tissue of arthritic rats during the course of the disease. By using immunohistochemical techniq ues, an abundant expression of all three TGF-beta isoforms and their r eceptors was observed in the arthritic synovia, an expression that inc reased with time after onset of disease. Antibodies to TGF-beta 1, TGF -beta 2, TGF-beta RI and TGF-beta RII stained blood vessels intensivel y, already at the early onset of inflammation, whereas the synovial li ning layer and chondrocytes expressed strong immunoreactivity later on in the inflammatory process. The most intense staining with these ant ibodies was detected in fibroblasts within fibrotic tissue, in particu lar at the cartilage-pannus junction. Interestingly, TGF-beta 3 only s tained macrophage-like cells and chondrocytes in the synovia. The data suggest that the abundant expression of TGF-beta 1, TGF-beta 2, TGF-b eta 3 as well as TGF-beta RI and TGF-beta RII in the synovia, is of pa thogenic importance in the development of CIA, although the question o f how the different TGF-beta isoforms may enhance or counteract differ ent arthritogenic events remains open.