Does transforming growth factor beta 1 play a role in the pathogenesis of chronic allograft rejection?

To investigate the potential role of Transforming Growth Factor beta 1 (TGF beta 1) in the pathogenesis of chronic allograft rejection, we studied TGF beta 1 expression in a rat aortic allograft model. mRNA and protein expres sion of total and endogenously active TGF beta 1 were analysed in infra-ren al orthotopic aortic syngeneic and allogeneic grafts and matched with the h istological appearances of the grafts, 2, 4 and 12 weeks post-transplantati on. Serum levels of TGF beta 1 were also measured. The level of TGF beta 1 model. RNA and protein expression appeared highest 2 and 4 weeks following transplantation in both syngeneic and allogeneic grafts, with significantly elevated levels of mRNA expression in the 2 week allograft specimens. Thes e time-points correlate histologically with maximal inflammatory cell infil tration of the grafts. By 12 weeks posttransplantation, TGF beta 1 mRNA exp ression is reduced in allogeneic grafts compared to syngeneic grafts. Howev er, detectable levels of total and endogenously active TGF beta 1 protein l evels in the allografts exceed those measured in the syngeneic grafts at th is time point. These results demonstrate the complex expression pattern of this growth factor during the progression of chronic rejection and suggest an aetiological link between TGF beta 1 and the process of accelerated graf t atherosclerosis.