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 expression of total and endogenously active TGF beta 1 were analysed in infra-renal orthotopic aortic syngeneic and allogeneic grafts and matched with the histological appearances of the grafts, 2, 4 and 12 weeks post-transplantation. Serum levels of TGF beta 1 were also measured. The level of TGF beta 1 m 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. These time-points correlate histologically with maximal inflammatory cell infiltration of the grafts. By 12 weeks post-transplantation, TGF beta 1 mRNA expression is reduced in allogeneic grafts compared to syngeneic grafts. However, detectable levels of total and endogenously active TGF beta 1 protein levels in the allografts exceed those measured in the syngeneic grafts at this 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 graft atherosclerosis.